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Liu Z, Zhao N, Liang L, Li M, Nie X, Wang Y, Liu Q, Zhou Q, Shu P. Evaluation of the anti-aging potential of acetyl tripeptide-30 citrulline in cosmetics. Int J Pharm 2024; 663:124557. [PMID: 39103061 DOI: 10.1016/j.ijpharm.2024.124557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 07/23/2024] [Accepted: 08/02/2024] [Indexed: 08/07/2024]
Abstract
Acetyl tripeptide-30 citrulline, a commercialized bio-active peptide, is widely used in anti-wrinkle formulations. Volunteer-based tests have demonstrated that topical application of products containing acetyl tripeptide-30 citrulline significantly reduces the visibility of stretch marks. However, there is still a lack of research dedicated to systematically and holistically evaluating its cosmetic properties and elucidating its mechanisms of action. In this study, we assessed the cosmetic potential of acetyl tripeptide-30 citrulline using human immortalized keratinocytes (HaCaT) and mouse embryonic fibroblasts (3T3). Our findings reveal that acetyl tripeptide-30 citrulline exhibits anti-inflammatory and antioxidant activities in skin cells, particularly effective against the inflammatory markers cyclooxygenase-2 (COX2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), and the extent of inhibition of reactive oxygen species (ROS) production ranged from 95 % to 340 %. Moreover, acetyl tripeptide-30 citrulline specifically up-regulates Collagen IV and down-regulates matrix metalloproteinase-9 (MMP9), enhances the expression of skin barrier proteins transglutaminase 1 (TGM1) and filaggrin (FLG), thereby demonstrating its reparative capabilities. Additionally, acetyl tripeptide-30 citrulline increases the expression of the water channel protein aquaporin 3 (AQP3), thus improving skin hydration function. These results substantiate the previously proclaimed cosmetic attributes of acetyl tripeptide-30 citrulline and support its efficacy as an anti-aging agent in dermatological applications.
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Affiliation(s)
- Zhao Liu
- HBN Research Institute and Biological Laboratory, Shenzhen Hujia Technology Co., Ltd., Shenzhen, Guangdong 518000, P.R. China.
| | - Nan Zhao
- HBN Research Institute and Biological Laboratory, Shenzhen Hujia Technology Co., Ltd., Shenzhen, Guangdong 518000, P.R. China
| | - Ling Liang
- HBN Research Institute and Biological Laboratory, Shenzhen Hujia Technology Co., Ltd., Shenzhen, Guangdong 518000, P.R. China
| | - Menggeng Li
- HBN Research Institute and Biological Laboratory, Shenzhen Hujia Technology Co., Ltd., Shenzhen, Guangdong 518000, P.R. China
| | - Xin Nie
- HBN Research Institute and Biological Laboratory, Shenzhen Hujia Technology Co., Ltd., Shenzhen, Guangdong 518000, P.R. China
| | - Yuan Wang
- HBN Research Institute and Biological Laboratory, Shenzhen Hujia Technology Co., Ltd., Shenzhen, Guangdong 518000, P.R. China
| | - Qin Liu
- HBN Research Institute and Biological Laboratory, Shenzhen Hujia Technology Co., Ltd., Shenzhen, Guangdong 518000, P.R. China
| | - Qi Zhou
- HBN Research Institute and Biological Laboratory, Shenzhen Hujia Technology Co., Ltd., Shenzhen, Guangdong 518000, P.R. China
| | - Peng Shu
- HBN Research Institute and Biological Laboratory, Shenzhen Hujia Technology Co., Ltd., Shenzhen, Guangdong 518000, P.R. China.
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Bordin ROA, Oliveira CD, Domeniconi RF. Immunolocalization of Aquaporin 1, 2, and 9 in Anuran Testis of the Neotropical Pointedbelly Frog Leptodactylus podicipinus. Curr Issues Mol Biol 2024; 46:9958-9969. [PMID: 39329946 PMCID: PMC11430573 DOI: 10.3390/cimb46090594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 08/28/2024] [Accepted: 08/30/2024] [Indexed: 09/28/2024] Open
Abstract
Many anuran survival strategies involve hydric regulation, and reproduction is not different. The aquaporin (AQP) family plays an important role in water transport and regulation in many tissues, including the male gonad. The testes undergo various stages of change during the reproductive cycle, and water balance is an important factor for ensuring reproductive success. Considering the relevance of water control in testicular development in anurans and the lack of research regarding the tissue localization of AQP in the male gonad, the present study investigated the expression of three AQPs (1, 2, and 9) in the testis of the neotropical anuran species Leptodactylus podicipinus during two different periods of the reproductive cycle (reproductive and non-reproductive). AQP1 and 2 immunoreactions were found in early germ cells, spermatozoa, Leydig cells, and Sertoli cells, which were more frequently expressed within the reproductive period. AQP1 was also found in the testicular blood vessels. AQP9 was identified predominantly in the epithelium of the intratesticular ducts of reproductive-period individuals. This study presents, for the first time, the localization of AQP1, AQP2, and AQP9 in the testes of an anuran species and the differences in their location during two distinct periods of the reproductive cycle.
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Affiliation(s)
- Rafael O A Bordin
- Department of Structural and Functional Biology, Universidade Estadual Paulista "Júlio de Mesquita Filho", Campus of Botucatu, São Paulo 18618689, SP, Brazil
| | - Classius de Oliveira
- Department of Biology, Universidade Estadual Paulista "Júlio de Mesquita Filho", Campus of São José do Rio Preto, São Paulo 15054000, SP, Brazil
| | - Raquel F Domeniconi
- Department of Structural and Functional Biology, Universidade Estadual Paulista "Júlio de Mesquita Filho", Campus of Botucatu, São Paulo 18618689, SP, Brazil
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Blumstein D, MacManes M. The multi-tissue gene expression and physiological responses of water deprived Peromyscus eremicus. BMC Genomics 2024; 25:770. [PMID: 39118009 PMCID: PMC11308687 DOI: 10.1186/s12864-024-10629-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Accepted: 07/17/2024] [Indexed: 08/10/2024] Open
Abstract
The harsh and dry conditions of desert environments have resulted in genomic adaptations, allowing for desert organisms to withstand prolonged drought, extreme temperatures, and limited food resources. Here, we present a comprehensive exploration of gene expression across five tissues (kidney, liver, lung, gastrointestinal tract, and hypothalamus) and 19 phenotypic measurements to explore the whole-organism physiological and genomic response to water deprivation in the desert-adapted cactus mouse (Peromyscus eremicus). The findings encompass the identification of differentially expressed genes and correlative analysis between phenotypes and gene expression patterns across multiple tissues. Specifically, we found robust activation of the vasopressin renin-angiotensin-aldosterone system (RAAS) pathways, whose primary function is to manage water and solute balance. Animals reduced food intake during water deprivation, and upregulation of PCK1 highlights the adaptive response to reduced oral intake via its actions aimed at maintained serum glucose levels. Even with such responses to maintain water balance, hemoconcentration still occurred, prompting a protective downregulation of genes responsible for the production of clotting factors while simultaneously enhancing angiogenesis which is thought to maintain tissue perfusion. In this study, we elucidate the complex mechanisms involved in water balance in the desert-adapted cactus mouse, P. eremicus. By prioritizing a comprehensive analysis of whole-organism physiology and multi-tissue gene expression in a simulated desert environment, we describe the complex response of regulatory processes.
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Affiliation(s)
- Danielle Blumstein
- Biomedical Sciences Department, University of New Hampshire, Molecular, Cellular, Durham, NH, DMB, 03824, USA.
| | - Matthew MacManes
- Biomedical Sciences Department, University of New Hampshire, Molecular, Cellular, Durham, NH, DMB, 03824, USA
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Blumstein DM, MacManes MD. When the tap runs dry: The multi-tissue gene expression and physiological responses of water deprived Peromyscus eremicus. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.01.22.576658. [PMID: 38328088 PMCID: PMC10849551 DOI: 10.1101/2024.01.22.576658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/09/2024]
Abstract
The harsh and dry conditions of desert environments have resulted in genomic adaptations, allowing for desert organisms to withstand prolonged drought, extreme temperatures, and limited food resources. Here, we present a comprehensive exploration of gene expression across five tissues (kidney, liver, lung, gastrointestinal tract, and hypothalamus) and 19 phenotypic measurements to explore the whole-organism physiological and genomic response to water deprivation in the desert-adapted cactus mouse (Peromyscus eremicus). The findings encompass the identification of differentially expressed genes and correlative analysis between phenotypes and gene expression patterns across multiple tissues. Specifically, we found robust activation of the vasopressin renin-angiotensin-aldosterone system (RAAS) pathways, whose primary function is to manage water and solute balance. Animals reduce food intake during water deprivation, and upregulation of PCK1 highlights the adaptive response to reduced oral intake via its actions aimed at maintained serum glucose levels. Even with such responses to maintain water balance, hemoconcentration still occurred, prompting a protective downregulation of genes responsible for the production of clotting factors while simultaneously enhancing angiogenesis which is thought to maintains tissue perfusion. In this study, we elucidate the complex mechanisms involved in water balance in the desert-adapted cactus mouse, P. eremicus. By prioritizing a comprehensive analysis of whole-organism physiology and multi-tissue gene expression in a simulated desert environment, we describe the complex and successful response of regulatory processes.
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Affiliation(s)
- Danielle M Blumstein
- University of New Hampshire, Molecular, Cellular, and Biomedical Sciences Department, Durham, NH 03824
| | - Matthew D MacManes
- University of New Hampshire, Molecular, Cellular, and Biomedical Sciences Department, Durham, NH 03824
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Akaishi T, Takahashi T, Misu T, Kaneko K, Takai Y, Nishiyama S, Ogawa R, Fujimori J, Ishii T, Aoki M, Fujihara K, Nakashima I. Difference in the Source of Anti-AQP4-IgG and Anti-MOG-IgG Antibodies in CSF in Patients With Neuromyelitis Optica Spectrum Disorder. Neurology 2021; 97:e1-e12. [PMID: 33980704 PMCID: PMC8312856 DOI: 10.1212/wnl.0000000000012175] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Accepted: 03/22/2021] [Indexed: 12/31/2022] Open
Abstract
Objective To elucidate the differences in the source and in the level of intrathecal synthesis between anti–aquaporin-4 antibodies (AQP4-IgG) and anti-myelin oligodendrocyte glycoprotein antibodies (MOG-IgG). Methods Thirty-eight patients with MOG-IgG–associated disease and 36 with AQP4-IgG–positive neuromyelitis optica spectrum disorders (NMOSD) were studied for the antibody titers in the sera and CSF simultaneously collected in the acute attacks. The quotients between CSF and serum levels of albumin, total immunoglobulin G, and each disease-specific antibody were calculated. Intrathecal production level in each disease-specific antibody was evaluated by calculating the antibody index from these quotients. Results Eleven of the 38 patients with MOG-IgG were positive for the antibody only in the CSF, while no patient with AQP4-IgG showed CSF-restricted AQP4-IgG. Blood-brain barrier compromise as shown by raised albumin quotients was seen in 75.0% of MOG-IgG–positive cases and 43.8% of AQP4-IgG–positive cases. Moreover, MOG-IgG quotients were >10 times higher than AQP4-IgG quotients (effect size r = 0.659, p < 0.0001). Elevated antibody index (>4.0) was confirmed in 12 of 21 with MOG-IgG, whereas it was seen only in 1 of 16 with AQP4-IgG (φ = 0.528, p < 0.0001). The CSF MOG-IgG titers (ρ = 0.519, p = 0.001) and antibody indexes for MOG-IgG (ρ = 0.472, p = 0.036) correlated with the CSF cell counts but not with clinical disability. Conclusions Intrathecal production of MOG-IgG may occur more frequently than that of AQP4-IgG. This finding implies the different properties of B-cell trafficking and antibody production between MOG-IgG–associated disease and AQP4-IgG–positive NMOSD.
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Affiliation(s)
- Tetsuya Akaishi
- From the Department of Neurology (T.A., T.T., T.M., K.K., Y.T., S.N., R.O., M.A.), Tohoku University Graduate School of Medicine; Department of Education and Support for Regional Medicine (T.A., T.I.), Tohoku University Hospital, Sendai; Department of Neurology (T.T.), National Hospital Organization Yonezawa National Hospital; Department of Neurology (J.F., I.N.), Tohoku Medical and Pharmaceutical University, Sendai; and Department of Multiple Sclerosis Therapeutics (K.F.), Fukushima Medical University, Japan.
| | - Toshiyuki Takahashi
- From the Department of Neurology (T.A., T.T., T.M., K.K., Y.T., S.N., R.O., M.A.), Tohoku University Graduate School of Medicine; Department of Education and Support for Regional Medicine (T.A., T.I.), Tohoku University Hospital, Sendai; Department of Neurology (T.T.), National Hospital Organization Yonezawa National Hospital; Department of Neurology (J.F., I.N.), Tohoku Medical and Pharmaceutical University, Sendai; and Department of Multiple Sclerosis Therapeutics (K.F.), Fukushima Medical University, Japan
| | - Tatsuro Misu
- From the Department of Neurology (T.A., T.T., T.M., K.K., Y.T., S.N., R.O., M.A.), Tohoku University Graduate School of Medicine; Department of Education and Support for Regional Medicine (T.A., T.I.), Tohoku University Hospital, Sendai; Department of Neurology (T.T.), National Hospital Organization Yonezawa National Hospital; Department of Neurology (J.F., I.N.), Tohoku Medical and Pharmaceutical University, Sendai; and Department of Multiple Sclerosis Therapeutics (K.F.), Fukushima Medical University, Japan
| | - Kimihiko Kaneko
- From the Department of Neurology (T.A., T.T., T.M., K.K., Y.T., S.N., R.O., M.A.), Tohoku University Graduate School of Medicine; Department of Education and Support for Regional Medicine (T.A., T.I.), Tohoku University Hospital, Sendai; Department of Neurology (T.T.), National Hospital Organization Yonezawa National Hospital; Department of Neurology (J.F., I.N.), Tohoku Medical and Pharmaceutical University, Sendai; and Department of Multiple Sclerosis Therapeutics (K.F.), Fukushima Medical University, Japan
| | - Yoshiki Takai
- From the Department of Neurology (T.A., T.T., T.M., K.K., Y.T., S.N., R.O., M.A.), Tohoku University Graduate School of Medicine; Department of Education and Support for Regional Medicine (T.A., T.I.), Tohoku University Hospital, Sendai; Department of Neurology (T.T.), National Hospital Organization Yonezawa National Hospital; Department of Neurology (J.F., I.N.), Tohoku Medical and Pharmaceutical University, Sendai; and Department of Multiple Sclerosis Therapeutics (K.F.), Fukushima Medical University, Japan
| | - Shuhei Nishiyama
- From the Department of Neurology (T.A., T.T., T.M., K.K., Y.T., S.N., R.O., M.A.), Tohoku University Graduate School of Medicine; Department of Education and Support for Regional Medicine (T.A., T.I.), Tohoku University Hospital, Sendai; Department of Neurology (T.T.), National Hospital Organization Yonezawa National Hospital; Department of Neurology (J.F., I.N.), Tohoku Medical and Pharmaceutical University, Sendai; and Department of Multiple Sclerosis Therapeutics (K.F.), Fukushima Medical University, Japan
| | - Ryo Ogawa
- From the Department of Neurology (T.A., T.T., T.M., K.K., Y.T., S.N., R.O., M.A.), Tohoku University Graduate School of Medicine; Department of Education and Support for Regional Medicine (T.A., T.I.), Tohoku University Hospital, Sendai; Department of Neurology (T.T.), National Hospital Organization Yonezawa National Hospital; Department of Neurology (J.F., I.N.), Tohoku Medical and Pharmaceutical University, Sendai; and Department of Multiple Sclerosis Therapeutics (K.F.), Fukushima Medical University, Japan
| | - Juichi Fujimori
- From the Department of Neurology (T.A., T.T., T.M., K.K., Y.T., S.N., R.O., M.A.), Tohoku University Graduate School of Medicine; Department of Education and Support for Regional Medicine (T.A., T.I.), Tohoku University Hospital, Sendai; Department of Neurology (T.T.), National Hospital Organization Yonezawa National Hospital; Department of Neurology (J.F., I.N.), Tohoku Medical and Pharmaceutical University, Sendai; and Department of Multiple Sclerosis Therapeutics (K.F.), Fukushima Medical University, Japan
| | - Tadashi Ishii
- From the Department of Neurology (T.A., T.T., T.M., K.K., Y.T., S.N., R.O., M.A.), Tohoku University Graduate School of Medicine; Department of Education and Support for Regional Medicine (T.A., T.I.), Tohoku University Hospital, Sendai; Department of Neurology (T.T.), National Hospital Organization Yonezawa National Hospital; Department of Neurology (J.F., I.N.), Tohoku Medical and Pharmaceutical University, Sendai; and Department of Multiple Sclerosis Therapeutics (K.F.), Fukushima Medical University, Japan
| | - Masashi Aoki
- From the Department of Neurology (T.A., T.T., T.M., K.K., Y.T., S.N., R.O., M.A.), Tohoku University Graduate School of Medicine; Department of Education and Support for Regional Medicine (T.A., T.I.), Tohoku University Hospital, Sendai; Department of Neurology (T.T.), National Hospital Organization Yonezawa National Hospital; Department of Neurology (J.F., I.N.), Tohoku Medical and Pharmaceutical University, Sendai; and Department of Multiple Sclerosis Therapeutics (K.F.), Fukushima Medical University, Japan
| | - Kazuo Fujihara
- From the Department of Neurology (T.A., T.T., T.M., K.K., Y.T., S.N., R.O., M.A.), Tohoku University Graduate School of Medicine; Department of Education and Support for Regional Medicine (T.A., T.I.), Tohoku University Hospital, Sendai; Department of Neurology (T.T.), National Hospital Organization Yonezawa National Hospital; Department of Neurology (J.F., I.N.), Tohoku Medical and Pharmaceutical University, Sendai; and Department of Multiple Sclerosis Therapeutics (K.F.), Fukushima Medical University, Japan
| | - Ichiro Nakashima
- From the Department of Neurology (T.A., T.T., T.M., K.K., Y.T., S.N., R.O., M.A.), Tohoku University Graduate School of Medicine; Department of Education and Support for Regional Medicine (T.A., T.I.), Tohoku University Hospital, Sendai; Department of Neurology (T.T.), National Hospital Organization Yonezawa National Hospital; Department of Neurology (J.F., I.N.), Tohoku Medical and Pharmaceutical University, Sendai; and Department of Multiple Sclerosis Therapeutics (K.F.), Fukushima Medical University, Japan
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Yagi R, Masuda T, Ogata S, Mori A, Ito S, Ohtsuki S. Proteomic Evaluation of Plasma Membrane Fraction Prepared from a Mouse Liver and Kidney Using a Bead Homogenizer: Enrichment of Drug-Related Transporter Proteins. Mol Pharm 2020; 17:4101-4113. [PMID: 32902293 DOI: 10.1021/acs.molpharmaceut.0c00547] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Quantifying the protein levels of drug transporters in plasma membrane fraction helps elucidate the function of these transporters. In this study, we conducted a proteomic evaluation of enriched drug-related transporter proteins in plasma membrane fraction prepared from mouse liver and kidney tissues using the membrane protein extraction kit and a bead homogenizer. Crude and plasma membrane fractions were prepared using either the Dounce or bead homogenizer, and protein levels were determined using quantitative proteomics. In liver tissues, the plasma membrane fractions were more enriched in transporter proteins than the crude membrane fractions; the average enrichment ratios of plasma-to-crude membrane fractions were 3.31 and 6.93 using the Dounce and bead homogenizers, respectively. The concentrations of transporter proteins in plasma membrane fractions determined using the bead homogenizer were higher than those determined using the Dounce homogenizer. Meanwhile, in kidney tissues, the plasma membrane fractions were enriched in transporters localized in the brush-border membrane to the same degree for both the homogenizers; however, the membrane fractions obtained using either homogenizer were not enriched in Na+/K+-ATPase and transporters localized in the basolateral membrane. These results indicate that fractionation, using the bead homogenizer, yielded transporter-enriched plasma membrane fractions from mouse liver and kidney tissues; however, no enrichment of basolateral transporters was observed in plasma membrane fractions prepared from kidney tissues.
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Affiliation(s)
- Ryotaro Yagi
- Department of Pharmaceutical Microbiology, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
| | - Takeshi Masuda
- Department of Pharmaceutical Microbiology, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.,Department of Pharmaceutical Microbiology, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.,Department of Pharmaceutical Microbiology, School of Pharmacy, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
| | - Seiryo Ogata
- Department of Pharmaceutical Microbiology, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
| | - Ayano Mori
- Department of Pharmaceutical Microbiology, School of Pharmacy, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
| | - Shingo Ito
- Department of Pharmaceutical Microbiology, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.,Department of Pharmaceutical Microbiology, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.,Department of Pharmaceutical Microbiology, School of Pharmacy, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
| | - Sumio Ohtsuki
- Department of Pharmaceutical Microbiology, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.,Department of Pharmaceutical Microbiology, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.,Department of Pharmaceutical Microbiology, School of Pharmacy, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
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Skowronska A, Tanski D, Jaskiewicz L, Skowronski MT. Modulation by steroid hormones and other factors on the expression of aquaporin-1 and aquaporin-5. VITAMINS AND HORMONES 2019; 112:209-242. [PMID: 32061342 DOI: 10.1016/bs.vh.2019.08.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Affiliation(s)
- A Skowronska
- Department of Human Physiology, School of Medicine, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland.
| | - D Tanski
- Department of Anatomy and Animal Physiology, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland
| | - L Jaskiewicz
- Department of Human Physiology, School of Medicine, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland
| | - M T Skowronski
- Veterinary Center, University of Nicolaus Copernicus, Torun, Poland
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Hou Z, Wei C. De novo comparative transcriptome analysis of a rare cicada, with identification of candidate genes related to adaptation to a novel host plant and drier habitats. BMC Genomics 2019; 20:182. [PMID: 30845906 PMCID: PMC6407286 DOI: 10.1186/s12864-019-5547-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2018] [Accepted: 02/20/2019] [Indexed: 01/18/2023] Open
Abstract
Background Although the importance of host plant chemistry in plant–insect interactions is widely recognized, our understanding about the genetic basis underlying the relationship between changes in midgut proteins and adaptation of plant-feeding insects to novel host plants and habitats is very limited. To address this knowledge gap, the transcriptional profiles of midguts among three populations of the cicada Subpsaltria yangi Chen were compared. Among which, the Hancheng (HC) and Fengxiang (FX) populations occurring in the Loess Plateau feed on Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chow, while the population occurring in a much drier habitat in the Helan (HL) Mountains is locally specialized on a chemically divergent plant, Ephedra lepidosperma C. Y. Cheng. Results Based on comparative analysis, 1826 (HL vs HC) differentially expressed genes (DEGs) and 723 DEGs (HL vs FX) were identified between the populations utilizing different host plants, including 20, 36, 2, 5 and 2 genes related to digestion, detoxification, oxidation-reduction, stress response and water-deprivation response, respectively, and 35 genes presumably associated with osmoregulation. However, only 183 DEGs were identified between the HC and FX populations, including two genes related to detoxification, two genes related to stress response, and one gene presumably associated with osmoregulation. These results suggest that the weakest expression differences were between the populations utilizing the same host plant and occurring in the closest habitats, which may help explain the metabolic mechanism of adaptation in S. yangi populations to novel host plants and new niches. Conclusions The observed differences in gene expression among S. yangi populations are consistent with the hypothesis that the host plant shift and habitat adaptation in the HL population was facilitated by differential regulation of genes related to digestion, detoxification, oxidation-reduction, stress response, water-deprivation response and osmoregulation. The results may inform future studies on the molecular mechanisms underlying the relationship between changes in midgut proteins and adaptation of herbivorous insects to novel host plants and new niches. Electronic supplementary material The online version of this article (10.1186/s12864-019-5547-y) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Zehai Hou
- State Key Laboratory of Crop Stress Biology for Arid Areas, and Key Laboratory of Plant Protection Resources and Pest Management, Ministry of Education, College of Plant Protection, Northwest A&F University, Yangling, 712100, Shaanxi, China
| | - Cong Wei
- State Key Laboratory of Crop Stress Biology for Arid Areas, and Key Laboratory of Plant Protection Resources and Pest Management, Ministry of Education, College of Plant Protection, Northwest A&F University, Yangling, 712100, Shaanxi, China.
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Lambert J, Mejia S, Vojdani A. Plant and human aquaporins: pathogenesis from gut to brain. Immunol Res 2018; 67:12-20. [DOI: 10.1007/s12026-018-9046-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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10
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Grüter T, Ayzenberg I, Gahlen A, Kneiphof J, Gold R, Kleiter I. Flaccid paralysis in neuromyelitis optica: An atypical presentation with possible involvement of the peripheral nervous system. Mult Scler Relat Disord 2018; 25:83-86. [PMID: 30056360 DOI: 10.1016/j.msard.2018.07.032] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2018] [Revised: 06/18/2018] [Accepted: 07/18/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Neuromyelitis optica spectrum disorders (NMOSD) typically lead to spastic paraparesis and spare the peripheral nervous system (PNS). CASE REPORT Here, we describe an anti-aquaporin-4-seropositive NMOSD patient suffering from acute transverse myelitis with painful, flaccid paralysis and incontinence of urine and feces. Due to the involvement of the PNS as indicated by electrodiagnostic examination, we verified the expression of aquaporin-4-channels on the proximal dorsal spinal radix of rats by staining rat tissue with human NMOSD serum. CONCLUSION This case suggests a manifestation of the proximal PNS in NMOSD. Thus, NMOSD should be considered as a differential diagnosis for patients presenting with signs of spinal cord disease and additional radicular involvement.
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Affiliation(s)
- Thomas Grüter
- Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.
| | - Ilya Ayzenberg
- Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany
| | - Anna Gahlen
- Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany
| | - Janina Kneiphof
- Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany
| | - Ralf Gold
- Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany
| | - Ingo Kleiter
- Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany
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11
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Schmidt V, Sturgis JN. Making Monomeric Aquaporin Z by Disrupting the Hydrophobic Tetramer Interface. ACS OMEGA 2017; 2:3017-3027. [PMID: 31457635 PMCID: PMC6641176 DOI: 10.1021/acsomega.7b00261] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Accepted: 06/14/2017] [Indexed: 05/31/2023]
Abstract
The assembly of integral membrane proteins depends on the packing of hydrophobic interfaces. The forces driving this packing remain unclear. In this study, we have investigated the effect of mutations in these hydrophobic interfaces on the structure and function of the tetrameric Escherichia coli water channel aquaporin Z (AqpZ). Among the variants, we have constructed several fail to form tetramers and are monomeric. In particular, both of the mutants which are expected to create interfacial cavities become monomeric. Furthermore, one of the mutations can be compensated by a second-site mutation. We suggest that the constraints imposed by the nature of the lipid solvent result in interfaces that respond differently to modifications of residues. Specifically, the large size and complex conformations of lipid molecules are unable to fill small interfacial holes. Further, we observe in AqpZ that there is a link between the oligomeric state and the water channel activity. This despite the robustness of both protein folding and topology, both of which remain unchanged by the mutations we introduce. We propose that this linkage may result from the specific modes of structural flexibility in the monomeric protein.
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12
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MacManes MD. Severe acute dehydration in a desert rodent elicits a transcriptional response that effectively prevents kidney injury. Am J Physiol Renal Physiol 2017; 313:F262-F272. [PMID: 28381460 DOI: 10.1152/ajprenal.00067.2017] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Revised: 03/28/2017] [Accepted: 03/28/2017] [Indexed: 12/14/2022] Open
Abstract
Animals living in desert environments are forced to survive despite severe heat, intense solar radiation, and both acute and chronic dehydration. These animals have evolved phenotypes that effectively address these environmental stressors. To begin to understand the ways in which the desert-adapted rodent Peromyscus eremicus survives, reproductively mature adults were subjected to 72 h of water deprivation, during which they lost, on average, 23% of their body weight. The animals reacted via a series of changes in the kidney, which included modulating expression of genes responsible for reducing the rate of transcription and maintaining water and salt balance. Extracellular matrix turnover appeared to be decreased, and apoptosis was limited. In contrast to the canonical human response, serum creatinine and other biomarkers of kidney injury were not elevated, suggesting that changes in gene expression related to acute dehydration may effectively prohibit widespread kidney damage in the cactus mouse.
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Affiliation(s)
- Matthew David MacManes
- Department of Molecular, Cellular, and Biomedical Sciences, University of New Hampshire, Durham, New Hampshire
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13
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Gleiser C, Wagner A, Fallier-Becker P, Wolburg H, Hirt B, Mack AF. Aquaporin-4 in Astroglial Cells in the CNS and Supporting Cells of Sensory Organs-A Comparative Perspective. Int J Mol Sci 2016; 17:E1411. [PMID: 27571065 PMCID: PMC5037691 DOI: 10.3390/ijms17091411] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Revised: 08/22/2016] [Accepted: 08/23/2016] [Indexed: 01/28/2023] Open
Abstract
The main water channel of the brain, aquaporin-4 (AQP4), is one of the classical water-specific aquaporins. It is expressed in many epithelial tissues in the basolateral membrane domain. It is present in the membranes of supporting cells in most sensory organs in a specifically adapted pattern: in the supporting cells of the olfactory mucosa, AQP4 occurs along the basolateral aspects, in mammalian retinal Müller cells it is highly polarized. In the cochlear epithelium of the inner ear, it is expressed basolaterally in some cells but strictly basally in others. Within the central nervous system, aquaporin-4 (AQP4) is expressed by cells of the astroglial family, more specifically, by astrocytes and ependymal cells. In the mammalian brain, AQP4 is located in high density in the membranes of astrocytic endfeet facing the pial surface and surrounding blood vessels. At these locations, AQP4 plays a role in the maintenance of ionic homeostasis and volume regulation. This highly polarized expression has not been observed in the brain of fish where astroglial cells have long processes and occur mostly as radial glial cells. In the brain of the zebrafish, AQP4 immunoreactivity is found along the radial extent of astroglial cells. This suggests that the polarized expression of AQP4 was not present at all stages of evolution. Thus, a polarized expression of AQP4 as part of a control mechanism for a stable ionic environment and water balanced occurred at several locations in supporting and glial cells during evolution. This initially basolateral membrane localization of AQP4 is shifted to highly polarized expression in astrocytic endfeet in the mammalian brain and serves as a part of the neurovascular unit to efficiently maintain homeostasis.
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Affiliation(s)
- Corinna Gleiser
- Institute of Clinical Anatomy and Cell Analysis, Eberhard Karls Universität Tübingen, 72074 Tübingen, Germany.
| | - Andreas Wagner
- Institute of Clinical Anatomy and Cell Analysis, Eberhard Karls Universität Tübingen, 72074 Tübingen, Germany.
| | - Petra Fallier-Becker
- Institute of Pathology and Neuropathology, Eberhard Karls Universität Tübingen, 72076 Tubingen, Germany.
| | - Hartwig Wolburg
- Institute of Pathology and Neuropathology, Eberhard Karls Universität Tübingen, 72076 Tubingen, Germany.
| | - Bernhard Hirt
- Institute of Clinical Anatomy and Cell Analysis, Eberhard Karls Universität Tübingen, 72074 Tübingen, Germany.
| | - Andreas F Mack
- Institute of Clinical Anatomy and Cell Analysis, Eberhard Karls Universität Tübingen, 72074 Tübingen, Germany.
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14
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Mobasheri A, Barrett-Jolley R. Aquaporin water channels in the mammary gland: from physiology to pathophysiology and neoplasia. J Mammary Gland Biol Neoplasia 2014; 19:91-102. [PMID: 24338153 PMCID: PMC3947960 DOI: 10.1007/s10911-013-9312-6] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2013] [Accepted: 11/13/2013] [Indexed: 12/21/2022] Open
Abstract
Aquaporins are membrane proteins that play fundamental roles in water and small solute transport across epithelial and endothelial barriers. Recent studies suggest that several aquaporin proteins are present in the mammary gland. Immunohistochemical techniques have confirmed the presence of aquaporin 1 (AQP1) and AQP3 water channels in rat, mouse, bovine and human mammary glands. Studies suggest that in addition to AQP1 and AQP3 AQP4, AQP5 and AQP7 proteins are expressed in different locations in the mammary gland. Aquaporins play key roles in tumor biology and are involved in cell growth, migration and formation of ascites via increased water permeability of micro-vessels. Emerging evidence suggests that expression of these proteins is altered in mammary tumors and in breast cancer cell lines although it is not yet clear whether this is a cause or a consequence of neoplastic development. This review analyzes the expression and potential functional roles of aquaporin water channels in the mammary gland. The physiological mechanisms involved in the transport of water and small solutes across mammary endothelial and epithelial barriers are discussed in the context of milk production and lactation. This paper also reviews papers from the recent cancer literature that implicate aquaporins in mammary neoplasia.
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Affiliation(s)
- Ali Mobasheri
- School of Pharmacy, University of Bradford, Richmond Road, Bradford, BD7 1DP, UK,
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15
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Tazawa M, Asai K, Iwasaki N. Characteristics of Hg- and Zn-sensitive Water Channels in the Plasma Membrane ofCharaCells*. ACTA ACUST UNITED AC 2014. [DOI: 10.1111/j.1438-8677.1996.tb00588.x] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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16
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Sekine S, Shimada Y, Nagata T, Sawada S, Yoshioka I, Matsui K, Moriyama M, Omura T, Osawa S, Shibuya K, Hashimoto I, Watanabe T, Hojo S, Hori R, Okumura T, Yoshida T, Tsukada K. Role of aquaporin-5 in gallbladder carcinoma. Eur Surg Res 2013; 51:108-17. [PMID: 24217644 DOI: 10.1159/000355675] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2013] [Accepted: 09/17/2013] [Indexed: 01/04/2023]
Abstract
BACKGROUND/PURPOSE Aquaporins (AQPs) are important in controlling bile formation. However, the exact role in human gallbladder carcinogenesis has not yet been defined. METHODS AQP-5-expressing gallbladder carcinoma (GBC) cell lines (NOZ) were transfected with anti-AQP-5 small interfering RNA (siRNA). Growth, migration, invasion assay, and drug susceptibility tests were performed. Next, microRNA (miRNA) expression was analyzed by miRNA oligo chip (3D-Gene®). AQP-5 and AQP-5-related miRNA target gene expressions were also analyzed using tissue microarray (TMA) in 44 GBC samples. RESULTS Treatment with AQP-5 siRNA decreased cell proliferation, migration, and invasion. On the other hand, those cells increased IC50 of gemcitabine. By performing miRNA assays, miR-29b, -200a, and -21 were shown to be highly overexpressed in cells treated with AQP-5 siRNA NOZ. When focusing on miR-21, phosphatase and tensin homolog (PTEN) was found to be a target of miR-21. In the TMA, AQP-5/PTEN coexpression was significantly associated with the depth of invasion and MIB-1 index (p = 0.003, 0.010). Survival of patients with a high AQP-5/PTEN coexpression was longer than that of patients with a low coexpression (p = 0.003). CONCLUSIONS Our result suggested that miR-21 and PTEN may contribute to the role of AQP-5 in GBC. AQP-5 and PTEN cascades are favorable biomarkers of GBC.
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Affiliation(s)
- S Sekine
- Department of Surgery and Science, University of Toyama, Toyama, Japan
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17
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Mack AF, Wolburg H. A novel look at astrocytes: aquaporins, ionic homeostasis, and the role of the microenvironment for regeneration in the CNS. Neuroscientist 2012; 19:195-207. [PMID: 22645111 DOI: 10.1177/1073858412447981] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Aquaporin-4 (AQP4) water channels are located at the basolateral membrane domain of many epithelial cells involved in ion transport and secretion. These epithelial cells separate fluid compartments by forming apical tight junctions. In the brain, AQP4 is located on astrocytes in a polarized distribution: At the border to blood vessels or the pial surface, its density is very high. During ontogeny and phylogeny, astroglial cells go through a stage of expressing tight junctions, separating fluid compartments differently than in adult mammals. In adult mammals, this barrier is formed by arachnoid, choroid plexus, and endothelial cells. The ontogenetic and phylogenetic barrier transition from glial to endothelial cells correlates with the regenerative capacity of neuronal structures: Glial cells forming tight junctions, and expressing no or unpolarized AQP4 are found in the fish optic nerve and the olfactory nerve in mammals both known for their regenerative ability. It is hypothesized that highly polarized AQP4 expression and the lack of tight junctions on astrocytes increase ionic homeostasis, thus improving neuronal performance possibly at the expense of restraining neurogenesis and regeneration.
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Affiliation(s)
- Andreas F Mack
- Institute of Anatomy, University of Tübingen, Tübingen, Germany.
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18
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Mobasheri A, Kendall BH, Maxwell JEJ, Sawran AV, German AJ, Marples D, Luck MR, Royal MD. Cellular localization of aquaporins along the secretory pathway of the lactating bovine mammary gland: an immunohistochemical study. Acta Histochem 2011; 113:137-49. [PMID: 19853284 DOI: 10.1016/j.acthis.2009.09.005] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2009] [Revised: 09/14/2009] [Accepted: 09/16/2009] [Indexed: 10/20/2022]
Abstract
In this study we examined the cellular localization of aquaporins (AQPs) along the secretory pathway of actively lactating bovine mammary glands using immunohistochemistry. Mammary tissues examined included secretory ducts and acini, gland cisterns, teats, stromal and adipose tissues. Aquaporin 1 (AQP1) was localized in capillary endothelia throughout the mammary gland in addition to myoepithelial cells underlying teat duct epithelia. AQP2 and AQP6 were not detected and AQP9 was found only in leukocytes. AQP3 and AQP4 were observed in selected epithelial cells in the teat, cistern and secretory tubuloalveoli. AQP5 immunopositivity was prominent in the cistern. AQP3 and AQP7 were found in smooth muscle bundles in the teat, secretory epithelial cells and duct epithelial cells. These immunohistochemical findings support a functional role for aquaporins in the transport of water and small solutes across endothelial and epithelial barriers in the mammary gland and in the production and secretion of milk.
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19
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Pandey RN, Yaganti S, Coffey S, Frisbie J, Alnajjar K, Goldstein D. Expression and immunolocalization of aquaporins HC-1, -2, and -3 in Cope's gray treefrog, Hyla chrysoscelis. Comp Biochem Physiol A Mol Integr Physiol 2010; 157:86-94. [DOI: 10.1016/j.cbpa.2010.04.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2010] [Revised: 04/08/2010] [Accepted: 04/09/2010] [Indexed: 01/13/2023]
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20
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Rauch C, Pluen A, Foster N, Loughna P, Mobasheri A, Lagadic-Gossmann D, Counillon L. On some aspects of the thermodynamic of membrane recycling mediated by fluid phase endocytosis: evaluation of published data and perspectives. Cell Biochem Biophys 2010; 56:73-90. [PMID: 20013072 DOI: 10.1007/s12013-009-9072-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
The theoretical and experimental description of fluid phase endocytosis (FPE) requires an asymmetry in phospholipid number between the two leaflets of the cell membrane, which provides the biomechanical torque needed to generate membrane budding. Although the motor force behind FPE is defined, its kinetic has yet to be determined. Based on a body of evidences suggesting that the mean surface tension is unlikely to be involved in endocytosis we decided to determine whether the cytosolic hydrostatic pressure could be involved, by considering a constant energy exchanged between the cytosol and the cell membrane. The theory is compared to existing experimental data obtained from FPE kinetic studies in living cells where altered phospholipid asymmetry or changes in the extracellular osmotic pressure have been investigated. The model demonstrates that FPE is dependent on the influx and efflux of vesicular volumes (i.e. vesicular volumes recycling) rather than the membrane tension of cells. We conclude that: (i) a relationship exists between membrane lipid number asymmetry and resting cytosolic pressure and (ii) the validity of Laplace's law is limited to cells incubated in a definite hypotonic regime. Finally, we discuss how the model could help clarifying elusive observations obtained from different fields and including: (a) the non-canonical shuttling of aquaporin in cells, (b) the relationship between high blood pressure and inflammation and (c) the mechanosensitivity of the sodium/proton exchanger.
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Affiliation(s)
- Cyril Rauch
- School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK.
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21
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Xia Y, Babitt JL, Bouley R, Zhang Y, Da Silva N, Chen S, Zhuang Z, Samad TA, Brenner GJ, Anderson JL, Hong CC, Schneyer AL, Brown D, Lin HY. Dragon enhances BMP signaling and increases transepithelial resistance in kidney epithelial cells. J Am Soc Nephrol 2010; 21:666-77. [PMID: 20167703 DOI: 10.1681/asn.2009050511] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
The neuronal adhesion protein Dragon acts as a bone morphogenetic protein (BMP) coreceptor that enhances BMP signaling. Given the importance of BMP signaling in nephrogenesis and its putative role in the response to injury in the adult kidney, we studied the localization and function of Dragon in the kidney. We observed that Dragon localized predominantly to the apical surfaces of tubular epithelial cells in the thick ascending limbs, distal convoluted tubules, and collecting ducts of mice. Dragon expression was weak in the proximal tubules and glomeruli. In mouse inner medullary collecting duct (mIMCD3) cells, Dragon generated BMP signals in a ligand-dependent manner, and BMP4 is the predominant endogenous ligand for the Dragon coreceptor. In mIMCD3 cells, BMP4 normally signaled through BMPRII, but Dragon enhanced its signaling through the BMP type II receptor ActRIIA. Dragon and BMP4 increased transepithelial resistance (TER) through the Smad1/5/8 pathway. In epithelial cells isolated from the proximal tubule and intercalated cells of collecting ducts, we observed coexpression of ActRIIA, Dragon, and BMP4 but not BMPRII. Taken together, these results suggest that Dragon may enhance BMP signaling in renal tubular epithelial cells and maintain normal renal physiology.
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Affiliation(s)
- Yin Xia
- Center for Systems Biology, Program in Membrane Biology and Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
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22
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Katkova LE, Solenov EI, Ivanova LN. The role of protein kinase C in the establishment of the mechanism of vasopressin antidiuretic action in the rat kidney during mammalian postnatal development. Russ J Dev Biol 2009. [DOI: 10.1134/s1062360409060058] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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23
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Pastor-Soler NM, Fisher JS, Sharpe R, Hill E, Van Hoek A, Brown D, Breton S. Aquaporin 9 expression in the developing rat epididymis is modulated by steroid hormones. Reproduction 2009; 139:613-21. [PMID: 19948840 DOI: 10.1530/rep-09-0284] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Fluid and solute transport across the epithelium of the male excurrent duct is important for sperm maturation and storage. Aquaporin 9 (AQP9), which allows permeation of water and neutral solutes, is abundant throughout the male reproductive tract, where it is expressed at the apical membrane of rat epididymal principal cells as early as at 1 week of age. We evaluated the effect of neonatal exposure to: 1) a GNRH antagonist (GNRHa); 2) diethylstilbestrol (DES); 3) ethinyl estradiol (EE); 4) DES plus testosterone (DES+TE); and 5) the anti-androgen flutamide on AQP9 expression in the epididymis of peripubertal rats. Control groups received the vehicle alone. In 25-day-old rats, quantification of the mean pixel intensity of immunofluorescence-stained sections showed a significant decrease in AQP9 staining in the apical membrane of epididymal principal cells after treatments with GNRHa, DES, or flutamide, compared to controls. These results were confirmed by western blotting. While EE induced a marked decrease in AQP9 levels by western blotting, the decrease in AQP9-associated fluorescence was not significant compared to controls. DES+TE-treated rats showed levels of AQP9 protein similar to controls, indicating maintenance of AQP9 expression by testosterone treatment in the presence of DES. Our data show that expression of AQP9 in the developing rat epididymis is downregulated by neonatal DES, GNRHa, EE, and flutamide, and that the effects mediated by estrogens can be prevented by testosterone administration.
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Affiliation(s)
- Núria M Pastor-Soler
- Program in Membrane Biology and Nephrology Division, Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
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24
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Van Hoek AN, Bouley R, Lu Y, Silberstein C, Brown D, Wax MB, Patil RV. Vasopressin-induced differential stimulation of AQP4 splice variants regulates the in-membrane assembly of orthogonal arrays. Am J Physiol Renal Physiol 2009; 296:F1396-404. [PMID: 19297454 DOI: 10.1152/ajprenal.00018.2009] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Aquaporin-4 (AQP4) is a basolateral water channel in collecting duct principal cells and assembles into orthogonal array particles (OAPs), the size of which appears to depend on relative expression levels of AQP4 splice variants. Because the higher-order organization of AQP4 was perturbed by vasopressin in Brattleboro rats and phosphorylation sites have been identified on AQP4, we investigated whether vasopressin and forskolin (Fk) affect AQP4 assembly and/or expression in LLC-PK(1) cells stably transfected with the AQP4 splice variant M23, which is responsible for formation of OAPs, and/or the splice variant M1, which does not form OAPs. Our data show that [lys(8)]-vasopressin (LVP) and Fk treatment led to differential increases in expression levels of M23-AQP4 and M1-AQP4 that varied as a function of incubation time. At early time points (day 1) expression of M1 was significantly stimulated (4.5-fold), over that of M23 (1.6-fold), but after 3 days the expression of M23 became predominant (4.1-fold) over that of M1 (1.9-fold). This pattern of stimulation was dependent on an intact AQP4 residue serine 111 and required protein synthesis. In cells expressing both M1 and M23 (M1/M23 approximately 1), with small sized OAPs at the membrane, the LVP/Fk-induced stimulation of M23 was modified and mimicked that of M1 when expressed alone, suggesting a dominant role for M1. In Brattleboro kidney inner medulla, an 8-day chronic exposure to the vasopressin agonist (dDAVP) led to reduction in M1 and a significant increase in M23 immunoblot staining (M1/M23 = 2/3 --> 1/4). These results indicate that AQP4 organization and expression are regulated by vasopressin in vivo and in vitro and demonstrate that the dominant role for M1 is restricted to a one-to-one interaction between AQP4 splice variants that regulates the membrane expression of OAPs.
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Affiliation(s)
- Alfred N Van Hoek
- Simches Research Center, 8.208, 185 Cambridge St., Boston, MA 02114, USA.
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25
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Les aquaporines présentes dans le rein. Nephrol Ther 2008; 4:562-7. [DOI: 10.1016/j.nephro.2008.03.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2007] [Revised: 03/28/2008] [Accepted: 03/29/2008] [Indexed: 11/15/2022]
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26
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Pietrement C, Da Silva N, Silberstein C, James M, Marsolais M, Van Hoek A, Brown D, Pastor-Soler N, Ameen N, Laprade R, Ramesh V, Breton S. Role of NHERF1, cystic fibrosis transmembrane conductance regulator, and cAMP in the regulation of aquaporin 9. J Biol Chem 2007; 283:2986-96. [PMID: 18055461 DOI: 10.1074/jbc.m704678200] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Water and solute transport across the plasma membrane of cells is a crucial biological function that is mediated mainly by aquaporins and aquaglyceroporins. The regulation of these membrane proteins is still incompletely understood. Using the male reproductive tract as a model system in which water and glycerol transport are critical for the establishment of fertility, we now report a novel pathway for the regulation of aquaporin 9 (AQP9) permeability. AQP9 is the major aquaglyceroporin of the epididymis, liver, and peripheral leukocytes, and its COOH-terminal portion contains a putative PDZ binding motif (SVIM). Here we show that NHERF1, cystic fibrosis transmembrane conductance regulator (CFTR), and AQP9 co-localize in the apical membrane of principal cells of the epididymis and the vas deferens, and that both NHERF1 and CFTR co-immunoprecipitate with AQP9. Overlay assays revealed that AQP9 binds to both the PDZ1 and PDZ2 domains of NHERF1, with an apparently higher affinity for PDZ1 versus PDZ2. Pull-down assays showed that the AQP9 COOH-terminal SVIM motif is essential for interaction with NHERF1. Functional assays on isolated tubules perfused in vitro showed a high permeability of the apical membrane to glycerol, which is inhibited by the AQP9 inhibitor, phloretin, and is markedly activated by cAMP. The CFTR inhibitors DPC, GlyH-101 and CFTRinh-172 all significantly reduced the cAMP-activated glycerol-induced cell swelling. We propose that CFTR is an important regulator of AQP9 and that the interaction between AQP9, NHERF1, and CFTR may facilitate the activation of AQP9 by cAMP.
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Affiliation(s)
- Christine Pietrement
- Center for Systems Biology, Program in Membrane Biology/Nephrology Division, Simches Research Center, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA
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27
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Buck TM, Wagner J, Grund S, Skach WR. A novel tripartite motif involved in aquaporin topogenesis, monomer folding and tetramerization. Nat Struct Mol Biol 2007; 14:762-9. [PMID: 17632520 DOI: 10.1038/nsmb1275] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2006] [Accepted: 06/22/2007] [Indexed: 12/24/2022]
Abstract
Aquaporin (AQP) folding in the endoplasmic reticulum is characterized by two distinct pathways of membrane insertion that arise from divergent residues within the second transmembrane segment. We now show that in AQP1 these residues (Asn49 and Lys51) interact with Asp185 at the C terminus of TM5 to form a polar, quaternary structural motif that influences multiple stages of folding. Asn49 and Asp185 form an intramolecular hydrogen bond needed for proper helical packing, monomer formation and function. In contrast, Lys51 interacts with Asp185 on an adjacent monomer to stabilize the AQP1 tetramer. Although these residues are unique to AQP1, they share a highly conserved architecture whose functional properties can be transferred to other family members. These findings suggest a general mechanism by which evolutionary divergence of membrane proteins can confer new functional properties via alternative folding pathways that give rise to a common final structure.
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Affiliation(s)
- Teresa M Buck
- Department of Biochemistry and Molecular Biology, Oregon Health & Sciences University, 3181 SW Sam Jackson Park Rd., Portland, Oregon 97239, USA
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28
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Da Silva N, Piétrement C, Brown D, Breton S. Segmental and cellular expression of aquaporins in the male excurrent duct. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 2006; 1758:1025-33. [PMID: 16935257 DOI: 10.1016/j.bbamem.2006.06.026] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/22/2005] [Revised: 06/07/2006] [Accepted: 06/08/2006] [Indexed: 01/05/2023]
Abstract
The male reproductive tract and accessory glands comprise a complex but interrelated system of tissues that are composed of many distinct cell types, all of which contribute to the ability of spermatozoa to carry out their ultimate function of fertilizing an oocyte. Spermatozoa undergo their final steps of maturation as they pass through the male excurrent duct, which includes efferent ducts, the epididymis and the vas deferens. The composition of the luminal environment in these organs is tightly regulated. Major fluid reabsorption occurs in efferent ducts and in the epididymis, and leads to a significant increase in sperm concentration. In the distal epididymis and vas deferens, fluid secretion controls the final fluidity of the luminal content. Therefore, the process of water movement in the excurrent duct is a crucial step for the establishment of male fertility. Aquaporins contribute to transepithelial water transport in many tissues, including the kidney, the brain, the eye and the respiratory tract. The present article reviews our current knowledge regarding the distribution and function of aquaporins in the male excurrent duct.
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Affiliation(s)
- Nicolas Da Silva
- Program in Membrane Biology-Nephrology Division, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02114-2790, USA
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Mobasheri A. Comment on: Cloning and characterization of porcine aquaporin 1 water channel expressed extensively in the gastrointestinal system. World J Gastroenterol 2006; 12:4437-9. [PMID: 16865795 PMCID: PMC4087764 DOI: 10.3748/wjg.v12.i27.4437] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Da Silva N, Silberstein C, Beaulieu V, Piétrement C, Van Hoek AN, Brown D, Breton S. Postnatal Expression of Aquaporins in Epithelial Cells of the Rat Epididymis1. Biol Reprod 2006; 74:427-38. [PMID: 16221990 DOI: 10.1095/biolreprod.105.044735] [Citation(s) in RCA: 67] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Abstract
The mammalian aquaporins (AQPs) are a family of 13 transmembrane channel proteins that are involved in the transport of water in numerous organs. In the male excurrent duct, the movement of fluid and solutes across the epithelium is essential for establishing the proper luminal environment in which sperm mature and are stored. AQP9 is abundantly expressed in the efferent ducts, the epididymis, and the vas deferens, where it could represent an important apical pathway for transmembrane water and solute movement. However, other organs in which water transport is critical, including the kidney, the lung, or the eye, express several different AQPs with a cell-specific pattern. To undertake a systematic analysis of the expression of known AQPs in the postnatal and adult rat epididymis, we examined the expression of their respective mRNAs in epithelial cells isolated by laser capture microdissection (LCM), and we determined their corresponding protein expression pattern by immunofluorescence and Western blotting. Our data show that, whereas AQP9 is the main AQP of the epididymis, the mRNA specific for Aqp2, 5, 7, and 11 are also expressed in epididymal epithelial cells. AQP5 protein colocalizes with AQP9 in the apical membrane of a subpopulation of principal cells in the corpus and cauda regions. Aqp2 mRNA was detected in epithelial cells after the second postnatal week and the amount significantly increased up to adulthood. However, AQP2 protein was detected only in the distal cauda of young rats (between the second and fourth postnatal week). No AQP2 protein was detected in the adult epididymis, indicating that posttranscriptional mechanisms are involved in the regulation of AQP2 expression. In addition, epididymal epithelial cells express significant amounts of the mRNAs coding for AQP7 and 11. No mRNA or protein for AQPs 0, 4, 6, and 8 were detectable in epithelial cells, and Aqp1 was detected in whole epididymal samples, but not in epithelial cells. Thanks to the recent development of microdissection technologies, our observations suggest that epididymal epithelial cells express several members of the AQP family with a region-specific pattern. AQPs may be involved not only in the transepithelial transport of water in the epididymis but also in the postnatal development of this organ, as suggested by the differential expression of AQP2.
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Affiliation(s)
- Nicolas Da Silva
- Massachusetts General Hospital, Program in Membrane Biology-Nephrology Division, Boston, Massachusetts 02114, USA.
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Witt M, Hummel T. Vomeronasal versus olfactory epithelium: is there a cellular basis for human vomeronasal perception? INTERNATIONAL REVIEW OF CYTOLOGY 2006; 248:209-59. [PMID: 16487792 DOI: 10.1016/s0074-7696(06)48004-9] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The vomeronasal organ (VNO) constitutes an accessory olfactory organ that receives chemical stimuli, pheromones, which elicit behavioral, reproductive, or neuroendocrine responses among individuals of the same species. In many macrosmatic animals, the morphological substrate constitutes a separate organ system consisting of a vomeronasal duct (ductus vomeronasalis, VND), equipped with chemosensory cells, and a vomeronasal nerve (nervus vomeronasalis, VNN) conducting information into the accessory olfactory bulb (AOB) in the central nervous system (CNS). Recent data require that the long-accepted dual functionality of a main olfactory system and the VNO be reexamined, since all species without a VNO are nevertheless sexually active, and species possessing a VNO also can sense other than "vomeronasal" stimuli via the vomeronasal epithelium (VNE). The human case constitutes a borderline situation, as its embryonic VNO anlage exerts a developmental track common to most macrosmatics, but later typical structures such as the VNN, AOB, and probably most of the chemoreceptor cells within the still existent VND are lost. This review also presents recent information on the VND including immunohistochemical expression of neuronal markers, intermediate filaments, lectins, integrins, caveolin, CD44, and aquaporins. Further, we will address the issue of human pheromone candidates.
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Affiliation(s)
- Martin Witt
- Department of Anatomy, University of Technology Dresden, Dresden, Germany
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Mobasheri A, Wray S, Marples D. Distribution of AQP2 and AQP3 water channels in human tissue microarrays. J Mol Histol 2005; 36:1-14. [PMID: 15703994 DOI: 10.1007/s10735-004-2633-4] [Citation(s) in RCA: 151] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2004] [Revised: 08/05/2004] [Indexed: 02/07/2023]
Abstract
The objective of this investigation was to use semi-quantitative immunohistochemistry to determine the distribution and expression levels of AQP2 and AQP3 proteins in normal human Tissue MicroArrays. Expression of the vasopressin regulated AQP2 was observed in a limited number of tissues. AQP2 was prominent in the apical and subapical plasma membranes of cortical and medullary renal collecting ducts. Surprisingly, weak AQP2 immunoreactivity was also noted in pancreatic islets, fallopian tubes and peripheral nerves. AQP2 was also localized to selected parts of the central nervous system (ependymal cell layer, subcortical white matter, hippocampus, spinal cord) and selected cells in the gastrointestinal system (antral and oxyntic gastric mucosa, small intestine and colon). These findings corroborate the restricted tissue distribution of AQP2. AQP3 was strongly expressed in many of the human tissues examined particularly in basolateral membranes of the distal nephron (medullary collecting ducts), distal colon, upper airway epithelia, transitional epithelium of the urinary bladder, tracheal, bronchial and nasopharyngeal epithelium, stratified squamous epithelial cells of the esophagus, and anus. AQP3 was moderately expressed in basolateral membranes of prostatic tubuloalveolar epithelium, pancreatic ducts, uterine endometrium, choroid plexus, articular chondrocytes, subchondral osteoblasts and synovium. Low AQP3 levels were also detected in skeletal muscle, cardiac muscle, gastric pits, seminiferous tubules, lymphoid vessels, salivary and endocrine glands, amniotic membranes, placenta and ovary. The abundance of basolateral AQP3 in epithelial tissues and its expression in many non-epithelial cells suggests that this aquaglyceroporin is a major participant in barrier hydration and water and osmolyte homeostasis in the human body.
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Affiliation(s)
- A Mobasheri
- Connective Tissue and Molecular Pathogenesis Research Groups, Faculty of Veterinary Science, University ofLiverpool, Liverpool, L69 7ZJ, UK
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Mobasheri A, Shakibaei M, Marples D. Immunohistochemical localization of aquaporin 10 in the apical membranes of the human ileum: a potential pathway for luminal water and small solute absorption. Histochem Cell Biol 2004; 121:463-71. [PMID: 15221416 DOI: 10.1007/s00418-004-0657-1] [Citation(s) in RCA: 60] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/29/2004] [Indexed: 01/02/2023]
Abstract
A new member of the aquaporin family (AQP10) has recently been identified in the human small intestine by molecular cloning and in situ hybridization. Ribonuclease protection assay and northern blotting have demonstrated that AQP10 is expressed in the human duodenum and jejunum. However, the subcellular distribution of the AQP10 protein and its plasma membrane polarization have not yet been established. The objective of this study was to determine the distribution of the AQP10 protein in the human ileum by immunohistochemistry and western blotting using a polyclonal antibody raised against a unique 17-amino acid peptide derived from the human AQP10 sequence. The distribution of the AQP1 and AQP3 proteins was also studied by immunohistochemical staining using affinity-purified polyclonal antibodies. Results revealed that the AQP10 protein is preferentially targeted to the apical membrane domain of absorptive intestinal epithelial cells, whereas AQP3 is located in the basolateral membrane of the cells and AQP1 expression is restricted to the mucosal microvascular endothelia. The presence of AQP10 in the apical membrane of intestinal villi suggests that this protein may represent an entry pathway for water and small solutes from the lumen across to the mucosal side.
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Affiliation(s)
- A Mobasheri
- Connective Tissue and Molecular Pathogenesis Research Groups, Faculty of Veterinary Science, University of Liverpool, L69 7ZJ, Liverpool, UK.
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Mobasheri A, Marples D. Expression of the AQP-1 water channel in normal human tissues: a semiquantitative study using tissue microarray technology. Am J Physiol Cell Physiol 2004; 286:C529-37. [PMID: 14592814 DOI: 10.1152/ajpcell.00408.2003] [Citation(s) in RCA: 153] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Aquaporin water channels are a family of membrane proteins that facilitate water movement across biological membranes. Aquaporin-1 (AQP-1) has been found to be important in osmotic water movement across cell membranes of epithelial and endothelial barriers. However, the distribution of AQP-1 in many normal human tissues is still unknown. The aim of this study was to use immunohistochemistry and semiquantitative histomorphometric analysis to determine the tissue distribution and relative expression of AQP-1 in normal human tissues using tissue microarray (TMA) technology. The normal human TMAs employed in this study included cardiovascular, respiratory, gastrointestinal, hepatic and pancreatobiliary, oral, salivary, nasal, mammary, fetal, endocrine, genital tract, central and peripheral nervous systems, urinary tract, skin, cartilage, and other soft connective tissues. Immunohistochemistry and semiquantitative histomorphometric analysis confirmed the presence of AQP-1 in endothelial barriers of almost all tissues and in many epithelial barriers. AQP-1 was highly expressed in the renal cortex, choroid plexus, and pancreatic ducts. AQP-1 expression levels were surprisingly high in the anus, gallbladder, and liver; moderate expression was also detected in the hippocampus and ependymal cells of the central nervous system. This is the first report of AQP-1 protein distribution in normal human TMAs. These findings confirm the presence of AQP-1 in human endothelia and selected water-transporting epithelia and several new locations, including mammary epithelium, articular chondrocytes, synoviocytes, and synovial microvessels where AQP-1 may be involved in milk production, chondrocyte volume regulation, synovial fluid secretion, and homeostasis, respectively.
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Affiliation(s)
- A Mobasheri
- Connective Tissue and Molecular Pathogenesis Research Groups, Faculty of Veterinary Science, University of Liverpool, Liverpool L69 7ZJ, United Kingdom.
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Amlal H, Ledoussal C, Sheriff S, Shull GE, Soleimani M. Downregulation of renal AQP2 water channel and NKCC2 in mice lacking the apical Na+-H+ exchanger NHE3. J Physiol 2003; 553:511-22. [PMID: 14500765 PMCID: PMC2343572 DOI: 10.1113/jphysiol.2003.053363] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Revised: 08/14/2003] [Accepted: 09/16/2003] [Indexed: 11/08/2022] Open
Abstract
The apical Na+-H+ exchanger NHE3 plays an important role in fluid reabsorption in the proximal tubule. However, whether its deletion alters the salt and water transport in the distal nephron remains unknown. To answer these questions, wild-type (Nhe3+/+) and NHE3 null mice (Nhe3-/-) were placed in metabolic cages and their water balance and urine osmolality were examined. Nhe3-/- mice demonstrated a significant polydipsia (P < 0.03) and polyuria (P < 0.04), with a lower urine osmolality (P < 0.003) as compared to Nhe3+/+ mice. Northern hybridization and immunoblotting studies indicated that the mRNA expression and protein abundance of the collecting duct (CD) water channel AQP2 decreased by 52 % (P < 0.0003) and 73 % (P < 0.003) in the cortex, and by 53 % and 54 % (P < 0.002) in the inner medulla (IM) of Nhe3-/- vs. Nhe3+/+ mice. The expression of AQP2 in the outer medulla (OM) remained unchanged. Further, the mRNA expression and protein abundance of the medullary thick ascending limb (mTAL) apical Na+-K+-2Cl- cotransporter (NKCC2) decreased by 52 % (P < 0.02) and 44 % (P < 0.01), respectively, in the OM of Nhe3-/- vs. Nhe3+/+ mice. The circulating plasma levels of vasopressin as well as the mRNA expression of vasopressin prohormone were significantly increased in Nhe3-/- vs. Nhe3+/+ mice (P < 0.05). Studies in mice treated with acetazolamide indicated that increased bicarbonate and fluid delivery to distal nephron did not alter the expression of NKCC2 in mTAL and decreased AQP2 protein only in OM but not in the cortex or IM. In conclusion, mice lacking the apical NHE3 have impairment in their water balance and urine osmolality, which correlates with the downregulation of AQP2 expression. These defects occur despite increased circulating levels of vasopressin. We propose that an ADH-independent mechanism is responsible for the downregulation of AQP2 and the resulting polyuria in NHE3 null mice.
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Affiliation(s)
- Hassane Amlal
- Departments of Medicine, University of Cincinnati School of Medicine, Cincinnati, OH 45267, USA.
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Hasegawa T, Tanii H, Suzuki M, Tanaka S. Regulation of water absorption in the frog skins by two vasotocin-dependent water-channel aquaporins, AQP-h2 and AQP-h3. Endocrinology 2003; 144:4087-96. [PMID: 12933683 DOI: 10.1210/en.2003-0418] [Citation(s) in RCA: 62] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
A new frog aquaporin (AQP) cDNA was cloned from a cDNA library constructed from the ventral skin of the tree frog Hyla japonica. This AQP (Hyla AQP-h2) consisted of 268 amino acid residues with a high homology to mammalian AQP2. The predicted amino acid sequence contained the two conserved Asn-Pro-Ala motifs found in all the major intrinsic protein family members and the putative six transmembrane domains. The sequence also contained a mercurial compound: cysteine, one potential N-glycosylation site at Asn-124, and a putative phosphorylation site recognized by protein kinase A at Ser-262. In a swelling assay using Xenopus oocytes, AQP-h2 facilitated water permeability, especially in response to cAMP. Expression of AQP-h2 mRNA was restricted to several tissues including the ventral skin, kidney, and urinary bladder; but with immunofluorescence staining using an antipeptide antibody (ST-140) against the AQP-h2 protein, immunopositive cells were found only in the ventral skin and urinary bladder. In the ventral pelvic skin, the label for AQP-h2 was localized in the entire plasma membrane of the granular cells beneath the outmost layer of the skin and in the basolateral membrane of the granular cells in this layer. In response to vasotocin, however, the label for AQP-h2 became more intense in the apical membrane in the granular cells of the outermost layer, similar to the case for the earlier studied AQP-h3, which was specifically expressed in the ventral skin. Taken together, these findings suggest that not only AQP-h3, but also AQP-h2 acts as a regulator of the water balance in this frog.
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Affiliation(s)
- Takahiro Hasegawa
- Department of Biology, Faculty of Science, Shizuoka University, Shizuoka 422-8529, Japan
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Peter K, Varga K, Bebok Z, McNicholas-Bevensee CM, Schwiebert L, Sorscher EJ, Schwiebert EM, Collawn JF. Ablation of internalization signals in the carboxyl-terminal tail of the cystic fibrosis transmembrane conductance regulator enhances cell surface expression. J Biol Chem 2002; 277:49952-7. [PMID: 12376531 DOI: 10.1074/jbc.m209275200] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel that undergoes endocytosis through clathrin-coated pits. Previously, we demonstrated that Y1424A is important for CFTR endocytosis (Prince, L. S., Peter, K., Hatton, S. R., Zaliauskiene, L., Cotlin, L. F., Clancy, J. P., Marchase, R. B., and Collawn, J. F. (1999) J. Biol. Chem. 274, 3602-3609). Here we show that a second substitution in the carboxyl-terminal tail of CFTR, I1427A, on Y1424A background more than doubles CFTR surface expression as monitored by surface biotinylation. Internalization assays indicate that enhanced surface expression of Y1424A,I1427A CFTR is caused by a 76% inhibition of endocytosis. Patch clamp recording of chloride channel activity revealed that there was a corresponding increase in chloride channel activity of Y1424A,I1427A CFTR, consistent with the elevated surface expression, and no change in CFTR channel properties. Y14124A showed an intermediate phenotype compared with the double mutation, both in terms of surface expression and chloride channel activity. Metabolic pulse-chase experiments demonstrated that the two mutations did not affect maturation efficiency or protein half-life. Taken together, our data show that there is an internalization signal in the COOH terminus of CFTR that consists of Tyr(1424)-X-X-Ile(1427) where both the tyrosine and the isoleucine are essential residues. This signal regulates CFTR surface expression but not CFTR biogenesis, degradation, or chloride channel function.
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Affiliation(s)
- Krisztina Peter
- Department of Cell Biology, Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, 1918 University Boulevard, Birmingham, AL 35294-0005, USA
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Werten PJ, Hasler L, Koenderink JB, Klaassen CH, de Grip WJ, Engel A, Deen PM. Large-scale purification of functional recombinant human aquaporin-2. FEBS Lett 2001; 504:200-5. [PMID: 11532454 DOI: 10.1016/s0014-5793(01)02703-x] [Citation(s) in RCA: 39] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The homotetrameric aquaporin-2 (AQP2) water channel is essential for the concentration of urine and of critical importance in diseases with water dysregulation, such as nephrogenic diabetes insipidus, congestive heart failure, liver cirrhosis and pre-eclampsia. The structure of human AQP2 is a prerequisite for understanding its function and for designing specific blockers. To obtain sufficient amounts of AQP2 for structural analyses, we have expressed recombinant his-tagged human AQP2 (HT-AQP2) in the baculovirus/insect cell system. Using the protocols outlined in this study, 0.5 mg of pure HT-AQP2 could be obtained per liter of bioreactor culture. HT-AQP2 had retained its homotetrameric structure and exhibited a single channel water permeability of 0.93+/-0.03x10(-13) cm3/s, similar to that of other AQPs. Thus, the baculovirus/insect cell system allows large-scale expression of functional recombinant human AQP2 that is suitable for structural studies.
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Affiliation(s)
- P J Werten
- Department of Cell Physiology, University of Nijmegen, The Netherlands
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Mitra AK. Three-Dimensional Organization of the aquaporin water channel: what can structure tell us about function? VITAMINS AND HORMONES 2001; 62:133-66. [PMID: 11345897 DOI: 10.1016/s0083-6729(01)62003-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/20/2023]
Affiliation(s)
- A K Mitra
- Department of Cell Biology, Scripps Research Institute, La Jolla, California 92037, USA
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Huang Y, Tracy R, Walsberg GE, Makkinje A, Fang P, Brown D, Van Hoek AN. Absence of aquaporin-4 water channels from kidneys of the desert rodent Dipodomys merriami merriami. Am J Physiol Renal Physiol 2001; 280:F794-802. [PMID: 11292621 DOI: 10.1152/ajprenal.2001.280.5.f794] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Recently, we found that aquaporin-4 (AQP4) is expressed in the S3 segment of renal proximal tubules of mice but not in rat proximal tubules. Because mice have relatively larger papillae than rats, it was proposed that the renal distribution of AQP4 in various species could be related to their maximum urinary concentrating ability. Therefore, kidneys and other tissues of Merriam's desert kangaroo rat, Dipodomys merriami merriami, which produce extremely concentrated urine (up to 5,000 mosmol/kgH(2)O), were examined for AQP4 expression and localization. Contrary to our expectation, AQP4 immunostaining was undetectable in any region of the kidney, and the absence of AQP4 protein was confirmed by Western blotting. By freeze fracture electron microscopy, orthogonal arrays of intramembraneous particles (OAPs) were not detectable in plasma membranes of principal cells and proximal tubules. However, AQP4 protein was readily detectable in gastric parietal and brain astroglial cells. Northern blotting failed to detect AQP4 mRNA in kangaroo rat kidneys, whereas both in situ hybridization and RT-PCR experiments did reveal AQP4 mRNA in collecting ducts and proximal tubules of the S3 segment. These results suggest that renal expression of AQP4 in the kangaroo rat kidney is regulated at the transcriptional or translational level, and the absence of AQP4 may be critical for the extreme urinary concentration that occurs in this species.
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Affiliation(s)
- Y Huang
- Renal Unit and Program in Membrane Biology, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA
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Sogami M, Era S, Murakami M, Seo Y, Watari H, Uyesaka N. Application of the transition state theory to water transport across cell membranes. BIOCHIMICA ET BIOPHYSICA ACTA 2001; 1511:42-8. [PMID: 11248203 DOI: 10.1016/s0005-2736(00)00384-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
We have applied the transition state theory of Eyring et al. (The Theory of Rate Processes, McGraw-Hill, 1941) to water transport across cell membranes. We have then evaluated free energy (Delta F(not equal)), enthalpy (Delta H(not equal)) and entropy (Delta S(not equal)) of activation for water permeation across membranes, such as Arbacia eggs, Xenopus oocytes with or without aquaporin water channels, mammalian erythrocytes, aquaporin proteoliposomes, liposomes and collodion membrane. Delta H(not equal) was found to be correlated with Delta S(not equal). This is so-called Delta H(not equal) and Delta S(not equal) compensation over the ranges of Delta H(not equal) and Delta S(not equal) from 2 to 22 kcal/mol and from -26 to 45 e.u., respectively, indicating that low Delta H(not equal) values correspond to negative Delta S(not equal). Large positive Delta S(not equal) and high Delta H(not equal) values might be accompanied by reversible breakage of secondary bonds in the membrane, presumably in membrane lipid bilayer. Largely negative Delta S(not equal) and low Delta H(not equal) values for aquaporin water channels, aquaporin proteoliposomes and porous collodion membrane could be explained by the immobilization of permeating water molecules in the membrane, i.e., the partial loss of rotational and/or translational freedoms of water molecules in water channels.
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Affiliation(s)
- M Sogami
- Department of Physiology, School of Health Sciences, Fujita Health University, Toyoake, Japan
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Abstract
The distinguishing feature of the mammalian outer hair cells (OHCs) is to elongate and shorten at acoustic frequencies, when their intracellular potential is changed. This "electromotility" or "electromechanics" depends critically on positive intracellular pressure (turgor), maintained by the inflow of water through yet uncharacterized water pathways. We measured the water volume flow, J(v), across the plasma membrane of isolated guinea pig and rat OHCs after osmotic challenges and estimated the osmotic water permeability coefficient, P(f), to be approximately 10(-2) cm/sec. This value is within the range reported for osmotic flow mediated by the water channel proteins, aquaporins. J(v) was inhibited by HgCl(2), which is known to block aquaporin-mediated water transport. P(f) values that were estimated for OHCs from neonatal rats were of the order of approximately 2 x 10(-3) cm/sec, equivalent to that of membranes lacking water channel proteins. In an immunofluorescence assay we showed that an anti-peptide antibody specific for aquaporins labels the lateral plasma membrane of the OHC in the region in which electromotility is generated. Using patch-clamp recording, we found that water influx into the OHC is regulated by intracellular voltage. We also found that the most pronounced increases of the electromotility-associated charge movement and of the expression of OHC water channels occur between postnatal days 8 and 12, preceding the onset of hearing function in the rat. Our data indicate that electromotility and water transport in OHCs may influence each other structurally and functionally.
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Foster W, Helm A, Turnbull I, Gulati H, Yang B, Verkman AS, Skach WR. Identification of sequence determinants that direct different intracellular folding pathways for aquaporin-1 and aquaporin-4. J Biol Chem 2000; 275:34157-65. [PMID: 10944517 DOI: 10.1074/jbc.m000165200] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Homologous aquaporin water channels utilize different folding pathways to acquire their transmembrane (TM) topology in the endoplasmic reticulum (ER). AQP4 acquires each of its six TM segments via cotranslational translocation events, whereas AQP1 is initially synthesized with four TM segments and subsequently converted into a six membrane-spanning topology. To identify sequence determinants responsible for these pathways, peptide segments from AQP1 and AQP4 were systematically exchanged. Chimeric proteins were then truncated, fused to a C-terminal translocation reporter, and topology was analyzed by protease accessibility. In each chimeric context, TM1 initiated ER targeting and translocation. However, AQP4-TM2 cotranslationally terminated translocation, while AQP1-TM2 failed to terminate translocation and passed into the ER lumen. This difference in stop transfer activity was due to two residues that altered both the length and hydrophobicity of TM2 (Asn(49) and Lys(51) in AQP1 versus Met(48) and Leu(50) in AQP4). A second peptide region was identified within the TM3-4 peptide loop that enabled AQP4-TM3 but not AQP1-TM3 to reinitiate translocation and cotranslationally span the membrane. Based on these findings, it was possible to convert AQP1 into a cotranslational biogenesis mode similar to that of AQP4 by substituting just two peptide regions at the N terminus of TM2 and the C terminus of TM3. Interestingly, each of these substitutions disrupted water channel activity. These data thus establish the structural basis for different AQP folding pathways and provide evidence that variations in cotranslational folding enable polytopic proteins to acquire and/or maintain primary sequence determinants necessary for function.
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Affiliation(s)
- W Foster
- Division of Molecular Medicine, Oregon Health Sciences University, Portland, Oregon 97201, USA
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Borok Z, Li X, Fernandes VF, Zhou B, Ann DK, Crandall ED. Differential regulation of rat aquaporin-5 promoter/enhancer activities in lung and salivary epithelial cells. J Biol Chem 2000; 275:26507-14. [PMID: 10849430 DOI: 10.1074/jbc.m910007199] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Aquaporin-5 (AQP5) is a water channel protein that is selectively expressed in respiratory, salivary, and lacrimal tissues. In order to establish the tissue-specific transcriptional programs that underlie its lung- and salivary-specific expression, a 4.5-kilobase pair DNA fragment encompassing the 5'-flanking region of the rat AQP5 gene has been characterized in detail. A major transcription start site utilized in lung and salivary glands has been localized downstream of a TATAA-like motif. Transient transfection assays of -4.3- and -1.7-AQP5-luciferase constructs in AQP5-expressing lung (MLE-15) and salivary (Pa-4) cells and nonexpressing fibroblast (NIH3T3) and epithelial (HeLa) cells demonstrate preferential transcriptional enhancement of reporter activities in MLE-15 and Pa-4 cells. Transient transfection assays of a series of 5' --> 3' deletion constructs of -4.3-AQP5-luciferase suggest that a common salivary and lung enhancer is located between nucleotides -274 and -139, and a lung-specific enhancer is located between nucleotides -894 and -710. There is one putative lung-specific repressor located in the region of nucleotides -1003/-894 and a common lung and salivary repressor located at nucleotides -503/-385. Moreover, 3' --> 5' deletions up to -171 and -127 base pairs almost abolish transcriptional activation in salivary and lung cells, respectively. Together, our findings indicate that the combination of enhancer/repressor elements within the proximal 5'-flanking region of rat AQP5 gene dictates its restricted expression in both lung and salivary cells.
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Affiliation(s)
- Z Borok
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Will Rogers Institute Pulmonary Research Center, Los Angeles, CA 90033, USA.
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45
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Snigirevskaya ES. Structural correlates of the transepithelial water transport. INTERNATIONAL REVIEW OF CYTOLOGY 2000; 198:203-75. [PMID: 10804464 DOI: 10.1016/s0074-7696(00)98006-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/16/2023]
Abstract
Transepithelial permeability is one of the fundamental problems in cell biology. Epithelial cell layers protect the organism from its environment and form a selective barrier to the exchange of molecules between the lumen of an organ and an underlying tissue. This chapter discusses some problems and analyzes the participation of intercellular junctions in the paracellular transport of water, migration of intramembrane particles in the apical membrane during its permeability changes for isotonic fluid in cells of leaky epithelia, insertion of water channels into the apical membrane and their cytoplasmic sources in cells of tight epithelia under ADH (antidiuretic hormone)-induced water flows, the osmoregulating function of giant vacuoles in the transcellular fluxes of hypotonic fluid across tight epithelia, and the role of actin filaments and microtubules in the transcellular transport of water across epithelia.
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Affiliation(s)
- E S Snigirevskaya
- Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia
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Abstract
The molecular mechanisms for regulating water balance in many tissues are unknown. Like the kidney, the eye contains multiple water channel proteins (aquaporins) that transport water through membranes, including two (AQP1 and AQP4) in the ciliary body, the site of aqueous humor production. Previous results from our laboratory demonstrated that water channel activity of AQP1 was significantly increased by protein kinase A (PKA) activators such as cyclic-AMP (cAMP) and forskolin. The purpose of this study is to determine whether PKA-dependent protein phosphorylation is involved in the regulation of water channel activity of AQP1. Results presented here suggest that catalytic subunit of protein kinase A significantly increased the amount of phosphorylated AQP1 protein. In addition, these results indicated that cAMP-responsive redistribution of AQP1 may be regulated by phosphorylation of AQP1. Moreover, they provide new insights on the molecular mechanisms for regulating water balance in several tissues involving rapid water transport such as ciliary epithelium. In addition, they suggest important potential roles for AQP1 in several clinical disorders involving rapid water transport such as glaucoma.
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Affiliation(s)
- Z Han
- Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA
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van Hoek AN, Ma T, Yang B, Verkman AS, Brown D. Aquaporin-4 is expressed in basolateral membranes of proximal tubule S3 segments in mouse kidney. Am J Physiol Renal Physiol 2000; 278:F310-6. [PMID: 10662735 DOI: 10.1152/ajprenal.2000.278.2.f310] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Because of the availability of knockout mouse models to examine renal transport mechanisms, it has become increasingly important to describe the cellular distribution of major renal transporters in mice. We have used immunocytochemistry and freeze-fracture electron microscopy to compare the renal distribution of aquaporin-4 (AQP4) with that previously described in rat. In rat kidney AQP4 is present exclusively in basolateral membranes of collecting duct principal cells. In mice, however, AQP4 was also detected by immunocytochemistry in basolateral membranes of proximal tubule S3 segments, and not detected in S1 and S2 segments of proximal tubule. Freeze-fracture electron microscopy revealed orthogonal arrays of intramembrane particles (OAPs) on the basolateral membranes of the S3 segment. In AQP4-knockout mice, immunostaining was absent and OAPs were found neither in collecting ducts nor in the S3 segment of the proximal tubule. The urinary concentrating capacity after deletion of both AQP1 and AQP4 was further reduced compared with that of AQP1 or AQP4 null mice, suggesting an additive effect of AQP1 and AQP4 in the concentrating mechanism. The functional significance of the apparent species-dependent expression of AQP4 in proximal tubules is unknown, but may relate to physiological differences between rats and mice.
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Affiliation(s)
- A N van Hoek
- Program in Membrane Biology/Renal Unit and Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
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Matsuzaki T, Suzuki T, Koyama H, Tanaka S, Takata K. Water channel protein AQP3 is present in epithelia exposed to the environment of possible water loss. J Histochem Cytochem 1999; 47:1275-86. [PMID: 10490456 DOI: 10.1177/002215549904701007] [Citation(s) in RCA: 131] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Aquaporins (AQPs) are membrane water channel proteins expressed in various tissues in the body. We surveyed the immunolocalization of AQP3, an isoform of the AQP family, in rat epithelial tissues. AQP3 was localized to many epithelial cells in the urinary, digestive, and respiratory tracts and in the skin. In the urinary tract, AQP3 was present at transitional epithelia. In the digestive tract, abundant AQP3 was found in the stratified epithelia in the upper part, from the oral cavity to the forestomach, and in the simple and stratified epithelia in the lower part, from the distal colon to the anal canal. In the respiratory tract, AQP3 was present in the pseudostratified ciliated epithelia from the nasal cavity to the intrapulmonary bronchi. In the skin, AQP3 was present in the epidermis. Interestingly, AQP3 was present at the basal aspects of the epithelia: in the basolateral membranes in the simple epithelia and in the multilayered epithelia at plasma membranes of the basal to intermediate cells. During development of the skin, AQP3 expression commenced late in fetal life. Because these AQP3-positive epithelia have a common feature, i.e., they are exposed to an environment of possible water loss, we propose that AQP3 could serve as a water channel to provide these epithelial cells with water from the subepithelial side to protect them against dehydration. (J Histochem Cytochem 47:1275-1286, 1999)
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Affiliation(s)
- T Matsuzaki
- Laboratory of Molecular and Cellular Morphology, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan
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Abstract
Fluid transport is a major function of the gastrointestinal (GI) tract with more than 9 litres of fluid being absorbed or secreted across epithelia in human salivary gland, stomach, the hepatobiliary tract, pancreas, small intestine and colon. This review evaluates the evidence that aquaporin-type water channels are involved in GI fluid transport. The aquaporins are a family of small ( approximately 30 kDa) integral membrane proteins that function as water channels. At least seven aquaporins are expressed in various tissues in the GI tract: AQP1 in intrahepatic cholangiocytes, AQP4 in gastric parietal cells, AQP3 and AQP4 in colonic surface epithelium, AQP5 in salivary gland, AQP7 in small intestine, AQP8 in liver, pancreas and colon, and AQP9 in liver. There are functional data suggesting that some GI cell types expressing aquaporins have high or regulated water permeability; however, there has been no direct evidence for a role of aquaporins in GI physiology. Recently, transgenic mice have been generated with selective deletions of various aquaporins. Preliminary evaluation of GI function suggests a role for AQP1 in dietary fat processing and AQP4 in colonic fluid absorption. Further study of aquaporin function in the GI tract should provide new insights into normal GI physiology and disease mechanisms, and may yield novel therapies to regulate fluid movement in GI diseases.
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Affiliation(s)
- T Ma
- Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, CA 94143-0521, USA
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Abstract
Since 1992 and the discovery of an MIP (major intrinsic protein of lens fiber cell) homologue protein that selectively permeates water, aquaporin (AQP), there has been an explosion of research in this field. Early research speculated that aquaporins played indispensible physiological roles in bacteria and plants, as well as in mammalian organs such as red blood cells, kidney, eye, brain and lung, where water transport rapidly takes place. Yet human subjects were identified who lacked AQP1 and yet had no apparent phenotypical changes clinically. To date 10 aquaporins have been discovered and a plethora of MIP members, and their prevalance in almost all organisms is a testament to their indispensible roles in the body, possibly as water and small neutral solute transporting channels. The recent localization of many different aquaporins in the same organ indicates that they may work cooperatively, which may partially explain the mystery of their physiological mechanism. Because the physiological roles of most aquaporins are currently only speculation, more extensive research is necessary to understand the exact function of each aquaporin.
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Affiliation(s)
- T Yamamoto
- Department of Pathology, Institute of Nephrology, Niigata University School of Medicine, Japan
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