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Boshoff A. Chaperonin: Co-chaperonin Interactions. Subcell Biochem 2023; 101:213-246. [PMID: 36520309 DOI: 10.1007/978-3-031-14740-1_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
Co-chaperonins function together with chaperonins to mediate ATP-dependent protein folding in a variety of cellular compartments. Chaperonins are evolutionarily conserved and form two distinct classes, namely, group I and group II chaperonins. GroEL and its co-chaperonin GroES form part of group I and are the archetypal members of this family of protein folding machines. The unique mechanism used by GroEL and GroES to drive protein folding is embedded in the complex architecture of double-ringed complexes, forming two central chambers that undergo conformational rearrangements that enable protein folding to occur. GroES forms a lid over the chamber and in doing so dislodges bound substrate into the chamber, thereby allowing non-native proteins to fold in isolation. GroES also modulates allosteric transitions of GroEL. Group II chaperonins are functionally similar to group I chaperonins but differ in structure and do not require a co-chaperonin. A significant number of bacteria and eukaryotes house multiple chaperonin and co-chaperonin proteins, many of which have acquired additional intracellular and extracellular biological functions. In some instances, co-chaperonins display contrasting functions to those of chaperonins. Human HSP60 (HSPD) continues to play a key role in the pathogenesis of many human diseases, in particular autoimmune diseases and cancer. A greater understanding of the fascinating roles of both intracellular and extracellular Hsp10 on cellular processes will accelerate the development of techniques to treat diseases associated with the chaperonin family.
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Affiliation(s)
- Aileen Boshoff
- Biotechnology Innovation Centre, Rhodes University, Makhanda/Grahamstown, South Africa.
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2
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Wei X, Su R, Yang M, Pan B, Lu J, Lin H, Shu W, Wang R, Xu X. Quantitative proteomic profiling of hepatocellular carcinoma at different serum alpha-fetoprotein level. Transl Oncol 2022; 20:101422. [PMID: 35430532 PMCID: PMC9034393 DOI: 10.1016/j.tranon.2022.101422] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 03/30/2022] [Accepted: 03/30/2022] [Indexed: 11/08/2022] Open
Abstract
Serum AFP equal to 400 ng/mL is a pivotal turning point not only in prognosis but also metabolic and invasion associated pathways. Adjacent noncancerous tissues are not biological normal components at protein level. Four druggable targets (C1QBP, HSPE1, CHDH, ITGAL) are identified as potential prognostic biomarkers in hepatocellular carcinoma. Purpose Hepatocellular carcinoma (HCC) is characterized by a poor long-term prognosis and high mortality rate. Serum alpha-fetoprotein (AFP) levels show great prognostic value in patients undergoing hepatectomy. This study aims to explore proteomic profiling in HCC samples based on AFP subgroups and identify potential key targets involved in HCC progression. Methods Twelve paired tumor and adjacent noncancerous tissue samples were collected from patients with HCC who underwent primary curative resection from January 2012 to December 2013. Clinical information was curated from four tissue microarrays to conduct survival analysis based on serum AFP levels. TMT-based quantitative proteomic analyses and bioinformatics analyses were performed to comprehensively profile molecular features. Immunohistochemistry was carried out to validate protein expression of identified targets. Kaplan-Meier survival analysis was performed to assess the overall survival and recurrence-free survival based on protein expressions. Results AFP (400 ng/mL) was a turning point in prognosis, metabolic- and invasion-associated pathways. The mass spectrometry analysis yielded a total of 5573 identified proteins. Annotations of 151 differentially expressed proteins in tumors and 95 proteins in paracancerous tissues (1.2-fold) showed similarities in biological processes, cellular components, molecular functions. Furthermore, differentially expressed hub proteins with five innovatively nominated druggable targets (C1QBP, HSPE1, GLUD2 for tumors and CHDH, ITGAL for paracancerous tissues), of which four (C1QBP, HSPE1, CHDH, ITGAL) targets were associated with poor overall survival (all Log-rank P < 0.05). Conclusions Our quantitative proteomics analyses identified four key prognostic biomarkers in HCC and provide opportunities for translational medicine and new treatment.
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3
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Pediatric Brain Tumors: Signatures from the Intact Proteome. Int J Mol Sci 2022; 23:ijms23063196. [PMID: 35328618 PMCID: PMC8949132 DOI: 10.3390/ijms23063196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 02/25/2022] [Accepted: 03/10/2022] [Indexed: 02/04/2023] Open
Abstract
The present investigation aimed to explore the intact proteome of tissues of pediatric brain tumors of different WHO grades and localizations, including medulloblastoma, pilocytic astrocytoma, and glioblastoma, in comparison with the available data on ependymoma, to contribute to the understanding of the molecular mechanisms underlying the onset and progression of these pathologies. Tissues have been homogenized in acidic water−acetonitrile solutions containing proteases inhibitors and analyzed by LC−high resolution MS for proteomic characterization and label-free relative quantitation. Tandem MS spectra have been analyzed by either manual inspection or software elaboration, followed by experimental/theoretical MS fragmentation data comparison by bioinformatic tools. Statistically significant differences in protein/peptide levels between the different tumor histotypes have been evaluated by ANOVA test and Tukey’s post-hoc test, considering a p-value > 0.05 as significant. Together with intact protein and peptide chains, in the range of molecular mass of 1.3−22.8 kDa, several naturally occurring fragments from major proteins, peptides, and proteoforms have been also identified, some exhibiting proper biological activities. Protein and peptide sequencing allowed for the identification of different post-translational modifications, with acetylations, oxidations, citrullinations, deamidations, and C-terminal truncations being the most frequently characterized. C-terminal truncations, lacking from two to four amino acid residues, particularly characterizing the β-thymosin peptides and ubiquitin, showed a different modulation in the diverse tumors studied. With respect to the other tumors, medulloblastoma, the most frequent malignant brain tumor of the pediatric age, was characterized by higher levels of thymosin β4 and β10 peptides, the latter and its des-IS form particularly marking this histotype. The distribution pattern of the C-terminal truncated forms was also different in glioblastoma, particularly underlying gender differences, according to the definition of male and female glioblastoma as biologically distinct diseases. Glioblastoma was also distinguished for the peculiar identification of the truncated form of the α-hemoglobin chain, lacking the C-terminal arginine, and exhibiting oxygen-binding and vasoconstrictive properties different from the intact form. The proteomic characterization of the undigested proteome, following the top-down approach, was challenging to originally investigate the post-translational events that differently characterize pediatric brain tumors. This study provides a contribution to elucidate the molecular profiles of the solid tumors most frequently affecting the pediatric age, and which are characterized by different grades of aggressiveness and localization.
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4
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Morelli AE, Sadovsky Y. Extracellular vesicles and immune response during pregnancy: A balancing act. Immunol Rev 2022; 308:105-122. [PMID: 35199366 DOI: 10.1111/imr.13074] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 02/09/2022] [Indexed: 12/15/2022]
Abstract
The mechanisms underlying maternal tolerance of the semi- or fully-allogeneic fetus are intensely investigated. Across gestation, feto-placental antigens interact with the maternal immune system locally within the trophoblast-decidual interface and distantly through shed cells and soluble molecules that interact with maternal secondary lymphoid tissues. The discovery of extracellular vesicles (EVs) as local or systemic carriers of antigens and immune-regulatory molecules has added a new dimension to our understanding of immune modulation prior to implantation, during trophoblast invasion, and throughout the course of pregnancy. New data on immune-regulatory molecules, located on EVs or within their cargo, suggest a role for EVs in negotiating immune tolerance during gestation. Lessons from the field of transplant immunology also shed light on possible interactions between feto-placentally derived EVs and maternal lymphoid tissues. These insights illuminate a potential role for EVs in major obstetrical disorders. This review provides updated information on intensely studied, pregnancy-related EVs, their cargo molecules, and patterns of fetal-placental-maternal trafficking, highlighting potential immune pathways that might underlie immune suppression or activation in gestational health and disease. Our summary also underscores the likely need to broaden the definition of the maternal-fetal interface to systemic maternal immune tissues that might interact with circulating EVs.
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Affiliation(s)
- Adrian E Morelli
- Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.,Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Yoel Sadovsky
- Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.,Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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5
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Gu LF, Chen JQ, Lin QY, Yang YZ. Roles of mitochondrial unfolded protein response in mammalian stem cells. World J Stem Cells 2021; 13:737-752. [PMID: 34367475 PMCID: PMC8316864 DOI: 10.4252/wjsc.v13.i7.737] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 05/13/2021] [Accepted: 06/15/2021] [Indexed: 02/06/2023] Open
Abstract
The mitochondrial unfolded protein response (UPRmt) is an evolutionarily conserved adaptive mechanism for improving cell survival under mitochondrial stress. Under physiological and pathological conditions, the UPRmt is the key to maintaining intracellular homeostasis and proteostasis. Important roles of the UPRmt have been demonstrated in a variety of cell types and in cell development, metabolism, and immune processes. UPRmt dysfunction leads to a variety of pathologies, including cancer, inflammation, neurodegenerative disease, metabolic disease, and immune disease. Stem cells have a special ability to self-renew and differentiate into a variety of somatic cells and have been shown to exist in a variety of tissues. These cells are involved in development, tissue renewal, and some disease processes. Although the roles and regulatory mechanisms of the UPRmt in somatic cells have been widely reported, the roles of the UPRmt in stem cells are not fully understood. The roles and functions of the UPRmt depend on stem cell type. Therefore, this paper summarizes the potential significance of the UPRmt in embryonic stem cells, tissue stem cells, tumor stem cells, and induced pluripotent stem cells. The purpose of this review is to provide new insights into stem cell differentiation and tumor pathogenesis.
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Affiliation(s)
- Li-Fang Gu
- Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Key Laboratory of Reproduction and Genetics in Ningxia, Department of Histology and Embryology, School of Basic Medicine, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Jia-Qi Chen
- Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Key Laboratory of Reproduction and Genetics in Ningxia, Department of Histology and Embryology, School of Basic Medicine, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Qing-Yin Lin
- Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Key Laboratory of Reproduction and Genetics in Ningxia, Department of Histology and Embryology, School of Basic Medicine, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Yan-Zhou Yang
- Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Key Laboratory of Reproduction and Genetics in Ningxia, Department of Histology and Embryology, School of Basic Medicine, Ningxia Medical University, Yinchuan 750001, Ningxia Hui Autonomous Region, China.
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Sarıkaya A, Aydın G, Özyüncü Ö, Şahin E, Uçkan-Çetinkaya D, Aerts-Kaya F. Comparison of immune modulatory properties of human multipotent mesenchymal stromal cells derived from bone marrow and placenta. Biotech Histochem 2021; 97:79-89. [PMID: 33641543 DOI: 10.1080/10520295.2021.1885739] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Multipotent mesenchymal stromal cells (MSC) can be isolated from many tissues, including bone marrow (BM) and placenta (PL). Human placenta can be obtained readily without invasive procedures. There may be differences, however, in differentiation capacity and immunomodulation by MSC isolated from BM or PL. The early pregnancy factor (heat shock protein 10; EPF/Hsp10) is a small protein that exhibits immunomodulatory properties. We compared BM- and PL-MSC, and assessed their efficacy for suppressing T-cell proliferation in vitro and the role of EPF/Hsp10 in this process. PL-MSC were collected from whole placenta after removal of the amniotic and chorionic membranes followed by serial enzymatic digestions. The PL-MSC were compared to BM-MSC, obtained from healthy donors. Differentiation capacity, cytokine secretion, expression and secretion of immunomodulatory molecules, immunophenotype and real time proliferation were assessed using cytokine arrays, ELISA assays, flow cytometry, immunohistochemical staining and western blotting. Whereas BM-MSC consisted of a homogeneous cell population with strong expression of mesenchymal markers, PL-MSC consisted of a mixed population of cells with variable CD73, CD90 and CD105 expression. PL-MSC exhibited a significantly greater proliferation rate than BM-MSC. The presence of both stem cells and more mature cells in the PL-MSC cultures resulted in decreased differentiation capacity and reduced efficacy of immune suppression in co-cultures with T-cells. Although robust intracellular expression of EPF/Hsp10 in both BM- and PL-MSC was observed, secretion of the protein in response to immune activating stimuli remained below detectable levels. Secretion of pro-inflammatory cytokines was significantly greater in BM-MSC than PL-MSC, whereas no difference was observed in the secretion of hematopoiesis supporting growth factors. Development of culture methods for isolation of pure populations of PL-MSC may improve the quality of the product and reproducibility of results.
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Affiliation(s)
- A Sarıkaya
- Department of Stem Cell Sciences, Graduate School of Health Sciences, Hacettepe University, Ankara, Turkey.,Center for Stem Cell Research and Development, Hacettepe University, Ankara, Turkey.,Department of Histology and Embryology, Institute of Health Sciences, Sakarya University, Sakarya, Turkey
| | - G Aydın
- Department of Stem Cell Sciences, Graduate School of Health Sciences, Hacettepe University, Ankara, Turkey.,Center for Stem Cell Research and Development, Hacettepe University, Ankara, Turkey
| | - Ö Özyüncü
- Department of Obstetrics and Gynecology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - E Şahin
- Department of Histology and Embryology, Institute of Health Sciences, Sakarya University, Sakarya, Turkey.,Department of Basic Medical Sciences, Faculty of Medicine, Sakarya University, Sakarya, Turkey
| | - D Uçkan-Çetinkaya
- Department of Stem Cell Sciences, Graduate School of Health Sciences, Hacettepe University, Ankara, Turkey.,Center for Stem Cell Research and Development, Hacettepe University, Ankara, Turkey.,Bone Marrow Transplantation Unit, Division of Pediatric Hematology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - F Aerts-Kaya
- Department of Stem Cell Sciences, Graduate School of Health Sciences, Hacettepe University, Ankara, Turkey.,Center for Stem Cell Research and Development, Hacettepe University, Ankara, Turkey
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Kovács ÁF, Fekete N, Turiák L, Ács A, Kőhidai L, Buzás EI, Pállinger É. Unravelling the Role of Trophoblastic-Derived Extracellular Vesicles in Regulatory T Cell Differentiation. Int J Mol Sci 2019; 20:ijms20143457. [PMID: 31337116 PMCID: PMC6678568 DOI: 10.3390/ijms20143457] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Revised: 07/09/2019] [Accepted: 07/11/2019] [Indexed: 12/30/2022] Open
Abstract
Regulatory T cells (Treg) are mandatory elements in the maintenance of human pregnancy, but their de novo differentiation has not been completely exposed. HSPE1 chaperone expressing trophoblast cells may have a role in it. Trophoblast-derived extracellular vesicles (EVs), either at the feto–maternal interface or in circulation, target CD4+ T cells. We hypothesized that HSPE1-associated trophoblastic cell line (BeWo)-derived EVs are active mediators of Treg cell differentiation. We proved at first that recombinant HSPE1 promote human Treg cell differentiation in vitro. Developing a CRISPR-Cas9 based HSPE1 knockout BeWo cell line we could also demonstrate, that EV-associated HSPE1 induces Treg development. Next-generation sequencing of miRNA cargo of BeWo-EVs characterized the regulatory processes of Treg polarization. By the use of single-cell transcriptomics analysis, seven Treg cell subtypes were distinguished and we demonstrated for the first time that the expression level of HSPE1 was Treg subtype dependent, and CAPG expression is characteristic to memory phenotype of T cells. Our data indicate that HSPE1 and CAPG may be used as markers for identification of Treg subtypes. Our results suggest, that trophoblastic-derived iEVs-associated HSPE1 and miRNA cargo have an important role in Treg cell expansion in vitro and HSPE1 is a useful marker of Treg subtype characterization.
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Affiliation(s)
- Árpád Ferenc Kovács
- Department of Genetics, Cell- and Immunobiology, Semmelweis University, H-1085 Budapest, Hungary.
| | - Nóra Fekete
- Department of Genetics, Cell- and Immunobiology, Semmelweis University, H-1085 Budapest, Hungary
| | - Lilla Turiák
- MS Proteomics Research Group, Research Centre for Natural Sciences, Hungarian Academy of Sciences, H-1051 Budapest, Hungary
| | - András Ács
- MS Proteomics Research Group, Research Centre for Natural Sciences, Hungarian Academy of Sciences, H-1051 Budapest, Hungary
| | - László Kőhidai
- Department of Genetics, Cell- and Immunobiology, Semmelweis University, H-1085 Budapest, Hungary
| | - Edit I Buzás
- Department of Genetics, Cell- and Immunobiology, Semmelweis University, H-1085 Budapest, Hungary
- MTA-SE Immune-Proteogenomics Extracellular Vesicle Research Group, H-1085 Budapest, Hungary
- HCEMM-SE Extracellular Vesicle Research Group, H-1085 Budapest, Hungary
| | - Éva Pállinger
- Department of Genetics, Cell- and Immunobiology, Semmelweis University, H-1085 Budapest, Hungary
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8
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Franier BDL, Thompson M. Early stage detection and screening of ovarian cancer: A research opportunity and significant challenge for biosensor technology. Biosens Bioelectron 2019; 135:71-81. [DOI: 10.1016/j.bios.2019.03.041] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Revised: 03/04/2019] [Accepted: 03/19/2019] [Indexed: 01/15/2023]
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9
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Fais S, Logozzi M, Alberti G, Campanella C. Exosomal Hsp60: A Tumor Biomarker? HEAT SHOCK PROTEIN 60 IN HUMAN DISEASES AND DISORDERS 2019. [DOI: 10.1007/978-3-030-23154-5_8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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10
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Hsp70 Interacts with Mitogen-Activated Protein Kinase (MAPK)-Activated Protein Kinase 2 To Regulate p38MAPK Stability and Myoblast Differentiation during Skeletal Muscle Regeneration. Mol Cell Biol 2018; 38:MCB.00211-18. [PMID: 30275345 DOI: 10.1128/mcb.00211-18] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Accepted: 09/26/2018] [Indexed: 12/24/2022] Open
Abstract
The regenerative process of injured muscle is dependent on the fusion and differentiation of myoblasts derived from muscle stem cells. Hsp70 is important for maintaining skeletal muscle homeostasis and regeneration, but the precise cellular mechanism remains elusive. In this study, we found that Hsp70 was upregulated during myoblast differentiation. Depletion or inhibition of Hsp70/Hsc70 impaired myoblast differentiation. Importantly, overexpression of p38 mitogen-activated protein kinase α (p38MAPKα) but not AKT1 rescued the impairment of myogenic differentiation in Hsp70- or Hsc70-depleted myoblasts. Moreover, Hsp70 interacted with MK2, a substrate of p38MAPK, to regulate the stability of p38MAPK. Knockdown of Hsp70 also led to downregulation of both MK2 and p38MAPK in intact muscles and during cardiotoxin-induced muscle regeneration. Hsp70 bound MK2 to regulate MK2-p38MAPK interaction in myoblasts. We subsequently identified the essential regions required for Hsp70-MK2 interaction. Functional analyses showed that MK2 is essential for both myoblast differentiation and skeletal muscle regeneration. Taken together, our findings reveal a novel role of Hsp70 in regulating myoblast differentiation by interacting with MK2 to stabilize p38MAPK.
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Park W, Srikanth K, Lim D, Park M, Hur T, Kemp S, Dessie T, Kim MS, Lee SR, te Pas MFW, Kim JM, Park JE. Comparative transcriptome analysis of Ethiopian indigenous chickens from low and high altitudes under heat stress condition reveals differential immune response. Anim Genet 2018; 50:42-53. [DOI: 10.1111/age.12740] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/16/2018] [Indexed: 01/22/2023]
Affiliation(s)
- W. Park
- Animal Genomics and Bioinformatics Division; National Institute of Animal Science, RDA; Wanju 55365 Korea
| | - K. Srikanth
- Animal Genomics and Bioinformatics Division; National Institute of Animal Science, RDA; Wanju 55365 Korea
| | - D. Lim
- Animal Genomics and Bioinformatics Division; National Institute of Animal Science, RDA; Wanju 55365 Korea
| | - M. Park
- Animal Breeding and Genomics Division; National Institute of Animal Science, RDA; Wanju 55365 Korea
| | - T. Hur
- Animal Genomics and Bioinformatics Division; National Institute of Animal Science, RDA; Wanju 55365 Korea
| | - S. Kemp
- Animal Biosciences; International Livestock Research Institute (ILRI); P.O. Box 30709 Nairobi 00100 Kenya
| | - T. Dessie
- Animal Biosciences; International Livestock Research Institute (ILRI); P.O. Box 5689 Addis Ababa Ethiopia
| | - M. S. Kim
- Department of Animal Science; College of Agriculture and Life Sciences; Chonnam National University; Republic of Korea Gwangju 61186 Korea
| | - S.-R. Lee
- Department of Agro-biotechnology Convergence; Jeonju University; Republic of Korea 55069 Jeonju Korea
| | - M. F. W. te Pas
- Animal Breeding and Genomics; Wageningen UR Livestock Research; 6700AH Wageningen The Netherlands
| | - J.-M. Kim
- Department of Animal Science and Technology; Chung-Ang University; Anseong Gyeonggi-do 17546 Korea
| | - J.-E. Park
- Animal Genomics and Bioinformatics Division; National Institute of Animal Science, RDA; Wanju 55365 Korea
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Tsai CH, Chen YT, Chang YH, Hsueh C, Liu CY, Chang YS, Chen CL, Yu JS. Systematic verification of bladder cancer-associated tissue protein biomarker candidates in clinical urine specimens. Oncotarget 2018; 9:30731-30747. [PMID: 30112103 PMCID: PMC6089400 DOI: 10.18632/oncotarget.24578] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2017] [Accepted: 02/20/2018] [Indexed: 12/29/2022] Open
Abstract
Bladder cancer biomarkers currently approved by the Food and Drug Administration are insufficiently reliable for use in non-invasive clinical diagnosis. Verification/validation of numerous biomarker candidates for BC detection is a crucial bottleneck for novel biomarker development. A multiplexed liquid chromatography multiple-reaction-monitoring mass spectrometry assay of 122 proteins, including 118 up-regulated tissue proteins, two known bladder cancer biomarkers and two housekeeping gene products, was successfully established for protein quantification in clinical urine specimens. Quantification of 122 proteins was performed on a large cohort of urine specimens representing a variety of conditions, including 142 hernia, 126 bladder cancer, 67 hematuria, and 59 urinary tract infection samples. ANXA3 (annexin A3) and HSPE1 (heat shock protein family E member 1), which showed the highest detection frequency in bladder cancer samples, were selected for further validation. Western blotting showed that urinary ANXA3 and HSPE1 protein levels were higher in bladder cancer samples than in hernia samples, and enzyme-linked immunosorbent assays confirmed a higher urinary concentration of HSPE1 in bladder cancer than in hernia, hematuria and urinary tract infection. Immunohistochemical analyses showed significantly elevated levels of HSPE1 in tumor cells compared with non-cancerous bladder epithelial cells, suggesting that HSPE1 could be a useful tumor tissue marker for the specific detection of bladder cancer. Collectively, our findings provide valuable information for future validation of potential biomarkers for bladder cancer diagnosis.
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Affiliation(s)
- Cheng-Han Tsai
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yi-Ting Chen
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Molecular Medicine Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Department of Nephrology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
| | - Ying-Hsu Chang
- Division of Urology, Department of Surgery, LinKou Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chuen Hsueh
- Molecular Medicine Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Department of Pathology, Chang Gung Memorial Hospital, Linkou, Chang Gung University, College of Medicine, Taoyuan, Taiwan
| | - Chung-Yi Liu
- Division of Urology, Department of Surgery, LinKou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Yu-Sun Chang
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Molecular Medicine Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Department of Otolaryngology - Head & Neck Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Chien-Lun Chen
- Department of Urology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Jau-Song Yu
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Molecular Medicine Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan.,Research Center for Food and Cosmetic Safety, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan
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13
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Zoppino FCM, Guerrero-Gimenez ME, Castro GN, Ciocca DR. Comprehensive transcriptomic analysis of heat shock proteins in the molecular subtypes of human breast cancer. BMC Cancer 2018; 18:700. [PMID: 29954368 PMCID: PMC6022707 DOI: 10.1186/s12885-018-4621-1] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2017] [Accepted: 06/20/2018] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Heat Shock Proteins (HSPs), a family of genes with key roles in proteostasis, have been extensively associated with cancer behaviour. However, the HSP family is quite large and many of its members have not been investigated in breast cancer (BRCA), particularly in relation with the current molecular BRCA classification. In this work, we performed a comprehensive transcriptomic study of the HSP gene family in BRCA patients from both The Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohorts discriminating the BRCA intrinsic molecular subtypes. METHODS We examined gene expression levels of 1097 BRCA tissue samples retrieved from TCGA and 1981 samples of METABRIC, focusing mainly on the HSP family (95 genes). Data were stratified according to the PAM50 gene expression (Luminal A, Luminal B, HER2, Basal, and Normal-like). Transcriptomic analyses include several statistical approaches: differential gene expression, hierarchical clustering and survival analysis. RESULTS Of the 20,531 analysed genes we found that in BRCA almost 30% presented deregulated expression (19% upregulated and 10% downregulated), while of the HSP family 25% appeared deregulated (14% upregulated and 11% downregulated) (|fold change| > 2 comparing BRCA with normal breast tissues). The study revealed the existence of shared HSP genes deregulated in all subtypes of BRCA while other HSPs were deregulated in specific subtypes. Many members of the Chaperonin subfamily were found upregulated while three members (BBS10, BBS12 and CCTB6) were found downregulated. HSPC subfamily had moderate increments of transcripts levels. Various genes of the HSP70 subfamily were upregulated; meanwhile, HSPA12A and HSPA12B appeared strongly downregulated. The strongest downregulation was observed in several HSPB members except for HSPB1. DNAJ members showed heterogeneous expression pattern. We found that 23 HSP genes correlated with overall survival and three HSP-based transcriptional profiles with impact on disease outcome were recognized. CONCLUSIONS We identified shared and specific HSP genes deregulated in BRCA subtypes. This study allowed the recognition of HSP genes not previously associated with BRCA and/or any cancer type, and the identification of three clinically relevant clusters based on HSPs expression patterns with influence on overall survival.
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Affiliation(s)
- Felipe C. M. Zoppino
- Laboratory of Oncology, Institute of Medicine and Experimental Biology of Cuyo (IMBECU), National Scientific and Technical Research Council (CONICET), Av. Dr. Ruiz Leal s/n, Parque General San Martín, 5500 Mendoza, Argentina
| | - Martin E. Guerrero-Gimenez
- Laboratory of Oncology, Institute of Medicine and Experimental Biology of Cuyo (IMBECU), National Scientific and Technical Research Council (CONICET), Av. Dr. Ruiz Leal s/n, Parque General San Martín, 5500 Mendoza, Argentina
| | - Gisela N. Castro
- Laboratory of Oncology, Institute of Medicine and Experimental Biology of Cuyo (IMBECU), National Scientific and Technical Research Council (CONICET), Av. Dr. Ruiz Leal s/n, Parque General San Martín, 5500 Mendoza, Argentina
| | - Daniel R. Ciocca
- Laboratory of Oncology, Institute of Medicine and Experimental Biology of Cuyo (IMBECU), National Scientific and Technical Research Council (CONICET), Av. Dr. Ruiz Leal s/n, Parque General San Martín, 5500 Mendoza, Argentina
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Thakur SS, Swiderski K, Ryall JG, Lynch GS. Therapeutic potential of heat shock protein induction for muscular dystrophy and other muscle wasting conditions. Philos Trans R Soc Lond B Biol Sci 2018; 373:rstb.2016.0528. [PMID: 29203713 DOI: 10.1098/rstb.2016.0528] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/18/2017] [Indexed: 02/03/2023] Open
Abstract
Duchenne muscular dystrophy is the most common and severe of the muscular dystrophies, a group of inherited myopathies caused by different genetic mutations leading to aberrant expression or complete absence of cytoskeletal proteins. Dystrophic muscles are prone to injury, and regenerate poorly after damage. Remorseless cycles of muscle fibre breakdown and incomplete repair lead to progressive and severe muscle wasting, weakness and premature death. Many other conditions are similarly characterized by muscle wasting, including sarcopenia, cancer cachexia, sepsis, denervation, burns, and chronic obstructive pulmonary disease. Muscle trauma and loss of mass and physical capacity can significantly compromise quality of life for patients. Exercise and nutritional interventions are unlikely to halt or reverse the conditions, and strategies promoting muscle anabolism have limited clinical acceptance. Heat shock proteins (HSPs) are molecular chaperones that help proteins fold back to their original conformation and restore function. Since many muscle wasting conditions have pathophysiologies where inflammation, atrophy and weakness are indicated, increasing HSP expression in skeletal muscle may have therapeutic potential. This review will provide evidence supporting HSP induction for muscular dystrophy and other muscle wasting conditions.This article is part of the theme issue 'Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective'.
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Affiliation(s)
- Savant S Thakur
- Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia
| | - Kristy Swiderski
- Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia
| | - James G Ryall
- Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia
| | - Gordon S Lynch
- Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia
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15
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Fan W, Fan SS, Feng J, Xiao D, Fan S, Luo J. Elevated expression of HSP10 protein inhibits apoptosis and associates with poor prognosis of astrocytoma. PLoS One 2017; 12:e0185563. [PMID: 29028811 PMCID: PMC5640213 DOI: 10.1371/journal.pone.0185563] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2017] [Accepted: 09/14/2017] [Indexed: 11/18/2022] Open
Abstract
Astrocytoma is the most common type of primary malignant brain tumor, with pretty lowly 5-year survival rate in patients. Although extended surgical removal of the tumor and postoperative chemotherapy/radiotherapy executed, still there is large recurrence rate, mainly because diffuse glioma tumor cells ubiquitously infiltrate into normal parenchyma. So it becomes a priority to hunt novel molecular and signaling pathway targets to suppress astrocyma progression. HSP10, an important member of Heat shock proteins (Hsps) family, classically works as molecular chaperone folding or degradating of target proteins. Evolutionarily, HSP10 is also reported to be involved in immunomodulation and tumor progression. Poly (ADP-ribose) polymerase (PARP), important in DNA repair, is one of the main cleavage targets of caspase. And cleaved PARP (c-PARP) can serve as a marker of cells undergoing apoptosis. So far, whether the expression of HSP10 or c-PARP is associated with clinicopathologic implication for astrocytoma has not been reported. Meanwhile, it is unclear about the relationship between HSP10 and cell apoptosis. The purpose of this research is to elucidate the association between the expression of HSP10 and c-PARP and clinicopathological characteristics of astrocytoma by immunohistochemistry. The results showed that positive percentage of high HSP10 expression in astrocytoma 42/103, 40.8%) was significantly higher than that in the non-tumor control brain tissues (8/43, 18.6%) (P = 0.01). While no apparent difference of high c-PARP expression existed between astrocytoma and non-tumor control brain tissues. Furthermore, elevated expression of HSP10 was negative related to low expression of c-PARP (r = -0.224, P = 0.023), indicating high expression of HSP10 in astrocytoma inhibited apoptosis process effectively. And overexpression of HSP10 was proved to be the independent poor prognostic factor for astrocytoma by multivariate analysis. Taken together, our results suggest that elevated expression of HSP10 protein inhibits apoptosis and associates with poor prognosis of astrocytoma.
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Affiliation(s)
- Weibing Fan
- Department of Neurology, The Third Hospital of Changsha, Changsha, Hunan, China
| | - Shuang-Shi Fan
- Department of Surgery, Children′s Hospital of Hunan Province, Changsha, Hunan, China
| | - Juan Feng
- Department of Pathology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Desheng Xiao
- Department of Pathology, Xiangya Hospital Central South University, Changsha, Hunan, China
| | - Songqing Fan
- Department of Pathology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- * E-mail: (SF); (JL)
| | - Jiadi Luo
- Department of Pathology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- * E-mail: (SF); (JL)
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16
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Caruso Bavisotto C, Cappello F, Macario AJL, Conway de Macario E, Logozzi M, Fais S, Campanella C. Exosomal HSP60: a potentially useful biomarker for diagnosis, assessing prognosis, and monitoring response to treatment. Expert Rev Mol Diagn 2017; 17:815-822. [PMID: 28718351 DOI: 10.1080/14737159.2017.1356230] [Citation(s) in RCA: 66] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Cell-to-cell communication is imperative for life and it is mediated by sending and receiving information via the secretion and subsequent receptor-mediated detection of biological molecules. Exosomes (EXs) secreted from cells to the extracellular environment play an important role in intercellular communication in normal and pathological conditions. Areas covered: New evidence indicates that tumor cells-derived EXs contribute to cancer progression through the modulation of tumor microenvironment. The exosomal heat shock protein 60 (HSP60) is very likely a key player in intercellular cross-talk, particularly during the progress of diseases, such as cancer. Many studies have focused on the extracellular roles played by HSP60 that pertain to cancer development and immune system stimulation. Our experimental data in vitro and in vivo demonstrated that HSP60 occurs on the surface of EXs secreted by tumour cells. Expert commentary: Exosomal HSP60 has great potential for clinical applications, as a 'liquid biopsy', including its use as biomarker for diagnostics, assessing prognosis, and monitoring disease progression and response to treatment, particularly in cancer.
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Affiliation(s)
- Celeste Caruso Bavisotto
- a Department of Experimental Biomedicine and Clinical Neurosciences, Section of Human Anatomy , University of Palermo , Palermo , Italy.,b Euro-Mediterranean Institute of Science and Technology (IEMEST) , Palermo , Italy
| | - Francesco Cappello
- a Department of Experimental Biomedicine and Clinical Neurosciences, Section of Human Anatomy , University of Palermo , Palermo , Italy.,b Euro-Mediterranean Institute of Science and Technology (IEMEST) , Palermo , Italy
| | - Alberto J L Macario
- b Euro-Mediterranean Institute of Science and Technology (IEMEST) , Palermo , Italy.,c Department of Microbiology and Immunology, School of Medicine , University of Maryland at Baltimore; and IMET , Baltimore , MD , USA
| | - Everly Conway de Macario
- b Euro-Mediterranean Institute of Science and Technology (IEMEST) , Palermo , Italy.,c Department of Microbiology and Immunology, School of Medicine , University of Maryland at Baltimore; and IMET , Baltimore , MD , USA
| | - Mariantonia Logozzi
- d Department of Therapeutic Research and Medicines Evaluation , National Institute of Health , Rome , Italy
| | - Stefano Fais
- b Euro-Mediterranean Institute of Science and Technology (IEMEST) , Palermo , Italy.,d Department of Therapeutic Research and Medicines Evaluation , National Institute of Health , Rome , Italy
| | - Claudia Campanella
- a Department of Experimental Biomedicine and Clinical Neurosciences, Section of Human Anatomy , University of Palermo , Palermo , Italy
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Filipović D, Costina V, Perić I, Stanisavljević A, Findeisen P. Chronic fluoxetine treatment directs energy metabolism towards the citric acid cycle and oxidative phosphorylation in rat hippocampal nonsynaptic mitochondria. Brain Res 2017; 1659:41-54. [DOI: 10.1016/j.brainres.2017.01.025] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2016] [Revised: 12/24/2016] [Accepted: 01/12/2017] [Indexed: 01/12/2023]
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18
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Chen JB, Neves MA, Thompson M. Biosensor surface attachment of the ovarian cancer biomarker HSP10 via His-tag modification. SENSING AND BIO-SENSING RESEARCH 2016. [DOI: 10.1016/j.sbsr.2016.10.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Rappa F, Pitruzzella A, Marino Gammazza A, Barone R, Mocciaro E, Tomasello G, Carini F, Farina F, Zummo G, Conway de Macario E, Macario AJ, Cappello F. Quantitative patterns of Hsps in tubular adenoma compared with normal and tumor tissues reveal the value of Hsp10 and Hsp60 in early diagnosis of large bowel cancer. Cell Stress Chaperones 2016; 21:927-33. [PMID: 27491302 PMCID: PMC5003810 DOI: 10.1007/s12192-016-0721-5] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Revised: 07/12/2016] [Accepted: 07/13/2016] [Indexed: 02/02/2023] Open
Abstract
Large bowel carcinogenesis involves accumulation of genetic alterations leading to transformation of normal mucosa into dysplasia and, lastly, adenocarcinoma. It is pertinent to elucidate the molecular changes occurring in the pre-neoplastic lesions to facilitate early diagnosis and treatment. Heat shock proteins (Hsps), many of which are molecular chaperones, are implicated in carcinogenesis, and their variations with tumor progression encourage their study as biomarkers. There are many reports on Hsps and cancer but none to our knowledge on their systematic quantification in pre-neoplastic lesions of the large bowel. We performed immunohistochemical determinations of Hsp10, Hsp60, Hsp70, and Hsp90 in biopsies of large bowel tubular adenomas with moderate grade of dysplasia and compared to normal mucosa and adenocarcinoma with a moderate grade of differentiation (G2). A significant elevation of Hsp10 and Hsp60 only, i.e., in the absence of elevation of Hsp70 or Hsp90, in both epithelium and lamina propria was found in tubular adenoma by comparison with normal mucosa. In contrast, adenocarcinoma was characterized by the highest levels of Hsp10 and Hsp60 in epithelium and lamina propria, accompanied by the highest levels of Hsp70 only in epithelium and of Hsp90 only in lamina propria, by comparison with normal and tubular adenoma counterparts. Hsp10 and Hsp60 are promising biomarkers for early diagnosis of tubular adenoma and for its differentiation from more advanced malignant lesions. Hsp10 and Hsp60 may be implicated in carcinogenesis from its very early steps and, thus, are potentially convenient targets for therapy.
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Affiliation(s)
- Francesca Rappa
- Department of Experimental Biomedicine and Clinical Neurosciences, Section of Human Anatomy, University of Palermo, Via del Vespro 129, 90127, Palermo, Italy.
- Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy.
| | - Alessandro Pitruzzella
- Department of Experimental Biomedicine and Clinical Neurosciences, Section of Human Anatomy, University of Palermo, Via del Vespro 129, 90127, Palermo, Italy
- Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy
| | - Antonella Marino Gammazza
- Department of Experimental Biomedicine and Clinical Neurosciences, Section of Human Anatomy, University of Palermo, Via del Vespro 129, 90127, Palermo, Italy
- Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy
| | - Rosario Barone
- Department of Experimental Biomedicine and Clinical Neurosciences, Section of Human Anatomy, University of Palermo, Via del Vespro 129, 90127, Palermo, Italy
- Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy
| | - Emanuele Mocciaro
- Department of Experimental Biomedicine and Clinical Neurosciences, Section of Human Anatomy, University of Palermo, Via del Vespro 129, 90127, Palermo, Italy
| | - Giovanni Tomasello
- Department of Experimental Biomedicine and Clinical Neurosciences, Section of Human Anatomy, University of Palermo, Via del Vespro 129, 90127, Palermo, Italy
- Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy
| | - Francesco Carini
- Department of Experimental Biomedicine and Clinical Neurosciences, Section of Human Anatomy, University of Palermo, Via del Vespro 129, 90127, Palermo, Italy
| | - Felicia Farina
- Department of Experimental Biomedicine and Clinical Neurosciences, Section of Human Anatomy, University of Palermo, Via del Vespro 129, 90127, Palermo, Italy
| | - Giovanni Zummo
- Department of Experimental Biomedicine and Clinical Neurosciences, Section of Human Anatomy, University of Palermo, Via del Vespro 129, 90127, Palermo, Italy
| | - Everly Conway de Macario
- Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy
- Department of Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore, Baltimore, MD, USA
- IMET, Columbus Center, Baltimore, MD, USA
| | - Alberto Jl Macario
- Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy
- Department of Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore, Baltimore, MD, USA
- IMET, Columbus Center, Baltimore, MD, USA
| | - Francesco Cappello
- Department of Experimental Biomedicine and Clinical Neurosciences, Section of Human Anatomy, University of Palermo, Via del Vespro 129, 90127, Palermo, Italy
- Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy
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20
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Ling Zheng L, Wang FY, Cong XX, Shen Y, Rao XS, Huang DS, Fan W, Yi P, Wang XB, Zheng L, Zhou YT, Luo Y. Interaction of Heat Shock Protein Cpn10 with the Cyclin E/Cdk2 Substrate Nuclear Protein Ataxia-Telangiectasia (NPAT) Is Involved in Regulating Histone Transcription. J Biol Chem 2015; 290:29290-300. [PMID: 26429916 PMCID: PMC4705935 DOI: 10.1074/jbc.m115.659201] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Indexed: 11/06/2022] Open
Abstract
Precise modulation of histone gene transcription is critical for cell cycle progression. As a direct substrate of Cyclin E/CDK2, nuclear protein ataxia-telangiectasia (NPAT) is a crucial factor in regulating histone transcription and cell cycle progression. Here we identified that Cpn10/HSPE, a 10-kDa heat shock protein, is a novel interacting partner of NPAT. A pool of Cpn10 is colocalized with NPAT foci during G1 and S phases in nuclei. Gain- and loss-of-function experiments unraveled an essential role of Cpn10 in histone transcription. A conserved DLFD motif within Cpn10 was critical for targeting NPAT and modulating histone transcription. More importantly, knockdown of Cpn10 disrupted the focus formation of both NPAT and FADD-like interleukin-1β-converting enzyme-associated huge protein without affecting Coilin-positive Cajal bodies. Finally, Cpn10 is important for S phase progression and cell proliferation. Taken together, our finding revealed a novel role of Cpn10 in the spatial regulation of NPAT signaling and disclosed a previously unappreciated link between the heat shock protein and histone transcription regulation.
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Affiliation(s)
- Li Ling Zheng
- From the Department of Biochemistry and Molecular Biology
| | - Fei Ya Wang
- From the Department of Biochemistry and Molecular Biology
| | - Xiao Xia Cong
- From the Department of Biochemistry and Molecular Biology, Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Center for Stem Cell and Regenerative Medicine, and
| | - Yue Shen
- Department of Orthopaedic Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
| | - Xi Sheng Rao
- From the Department of Biochemistry and Molecular Biology, Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Center for Stem Cell and Regenerative Medicine, and
| | - Dao Sheng Huang
- From the Department of Biochemistry and Molecular Biology, Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Center for Stem Cell and Regenerative Medicine, and
| | - Wei Fan
- From the Department of Biochemistry and Molecular Biology, Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Center for Stem Cell and Regenerative Medicine, and
| | - Peng Yi
- From the Department of Biochemistry and Molecular Biology, Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Center for Stem Cell and Regenerative Medicine, and
| | - Xin Bao Wang
- the Department of Abdominal Tumor Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China, and
| | - Lei Zheng
- the Department of Surgery and Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231
| | - Yi Ting Zhou
- From the Department of Biochemistry and Molecular Biology, Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Center for Stem Cell and Regenerative Medicine, and
| | - Yan Luo
- From the Department of Biochemistry and Molecular Biology,
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21
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Herrero Ó, Planelló R, Morcillo G. The plasticizer benzyl butyl phthalate (BBP) alters the ecdysone hormone pathway, the cellular response to stress, the energy metabolism, and several detoxication mechanisms in Chironomus riparius larvae. CHEMOSPHERE 2015; 128:266-277. [PMID: 25725395 DOI: 10.1016/j.chemosphere.2015.01.059] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/28/2014] [Revised: 01/25/2015] [Accepted: 01/27/2015] [Indexed: 06/04/2023]
Abstract
Butyl benzyl phthalate (BBP) has been extensively used worldwide as a plasticizer in the polyvinyl chloride (PVC) industry and the manufacturing of many other products, and its presence in the aquatic environment is expected for decades. In the present study, the toxicity of BBP was investigated in Chironomus riparius aquatic larvae. The effects of acute 24-h and 48-h exposures to a wide range of BBP doses were evaluated at the molecular level by analysing changes in genes related to the stress response, the endocrine system, the energy metabolism, and detoxication pathways, as well as in the enzyme activity of glutathione S-transferase. BBP caused a dose and time-dependent toxicity in most of the selected biomarkers. 24-h exposures to high doses affected larval survival and lead to a significant response of several heat-shock genes (hsp70, hsp40, and hsp27), and to a clear endocrine disrupting effect by upregulating the ecdysone receptor gene (EcR). Longer treatments with low doses triggered a general repression of transcription and GST activity. Furthermore, delayed toxicity studies were specially relevant, since they allowed us to detect unpredictable toxic effects, not immediately manifested after contact with the phthalate. This study provides novel and interesting results on the toxic effects of BBP in C. riparius and highlights the suitability of this organism for ecotoxicological risk assessment, especially in aquatic ecosystems.
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Affiliation(s)
- Óscar Herrero
- Grupo de Biología y Toxicología Ambiental, Facultad de Ciencias, Universidad Nacional de Educación a Distancia, UNED, Paseo de la Senda del Rey 9, 28040 Madrid, Spain.
| | - Rosario Planelló
- Grupo de Biología y Toxicología Ambiental, Facultad de Ciencias, Universidad Nacional de Educación a Distancia, UNED, Paseo de la Senda del Rey 9, 28040 Madrid, Spain.
| | - Gloria Morcillo
- Grupo de Biología y Toxicología Ambiental, Facultad de Ciencias, Universidad Nacional de Educación a Distancia, UNED, Paseo de la Senda del Rey 9, 28040 Madrid, Spain.
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Abstract
Co-chaperonins function together with chaperonins to mediate ATP-dependant protein folding in a variety of cellular compartments. GroEL and its co-chaperonin GroES are the only essential chaperones in Escherichia coli and are the archetypal members of this family of protein folding machines. The unique mechanism used by GroEL and GroES to drive protein folding is embedded in the complex architecture of double-ringed complexes, forming two central chambers that undergo structural rearrangements as part of the folding mechanism. GroES forms a lid over the chamber, and in doing so dislodges bound substrate into the chamber, thereby allowing non-native proteins to fold in isolation. GroES also modulates allosteric transitions of GroEL. A significant number of bacteria and eukaryotes house multiple chaperonin and co-chaperonin proteins, many of which have acquired additional intracellular and extracellular biological functions. In some instances co-chaperonins display contrasting functions to those of chaperonins. Human Hsp60 continues to play a key role in the pathogenesis of many human diseases, in particular autoimmune diseases and cancer. A greater understanding of the fascinating roles of both intracellular and extracellular Hsp10, in addition to its role as a co-chaperonin, on cellular processes will accelerate the development of techniques to treat diseases associated with the chaperonin family.
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Affiliation(s)
- Aileen Boshoff
- Biomedical Biotechnology Research Unit (BioBRU), Biotechnology Innovation Centre, Rhodes University, PO Box 94, 6140, Grahamstown, South Africa,
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23
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Suganya N, Bhakkiyalakshmi E, Subin TS, Krishnamurthi K, Devi SS, Lau K, Sekar TV, Paulmurugan R, Ramkumar KM. Proteomic Identification of Pterostilbene-Mediated Anticancer Activities in HepG2 Cells. Chem Res Toxicol 2014; 27:1243-52. [DOI: 10.1021/tx5001392] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Affiliation(s)
- N. Suganya
- SRM
Research Institute, SRM University, Kattankulathur, Tamilnadu, India
| | - E. Bhakkiyalakshmi
- SRM
Research Institute, SRM University, Kattankulathur, Tamilnadu, India
| | - T. S. Subin
- Environmental
Health Division, National Environmental Engineering Research Institute, Nagpur, India
| | - K. Krishnamurthi
- Environmental
Health Division, National Environmental Engineering Research Institute, Nagpur, India
| | - S. Saravana Devi
- Environmental
Health Division, National Environmental Engineering Research Institute, Nagpur, India
| | - K. Lau
- Department
of Radiology, Stanford University School of Medicine, 3155 Porter
Drive, Stanford, California 94305, United States
| | - T. V. Sekar
- Department
of Radiology, Stanford University School of Medicine, 3155 Porter
Drive, Stanford, California 94305, United States
| | - R. Paulmurugan
- Department
of Radiology, Stanford University School of Medicine, 3155 Porter
Drive, Stanford, California 94305, United States
| | - K. M. Ramkumar
- SRM
Research Institute, SRM University, Kattankulathur, Tamilnadu, India
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24
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The potential role of heat shock proteins in acute spinal cord injury. EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2014; 23:1480-90. [DOI: 10.1007/s00586-014-3214-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/04/2013] [Revised: 11/26/2013] [Accepted: 01/08/2014] [Indexed: 12/19/2022]
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De novo assembly and characterization of the global transcriptome for Rhyacionia leptotubula using Illumina paired-end sequencing. PLoS One 2013; 8:e81096. [PMID: 24278383 PMCID: PMC3837686 DOI: 10.1371/journal.pone.0081096] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2013] [Accepted: 10/09/2013] [Indexed: 12/21/2022] Open
Abstract
Background The pine tip moth, Rhyacionia leptotubula (Lepidoptera: Tortricidae) is one of the most destructive forestry pests in Yunnan Province, China. Despite its importance, less is known regarding all aspects of this pest. Understanding the genetic information of it is essential for exploring the specific traits at the molecular level. Thus, we here sequenced the transcriptome of R. leptotubula with high-throughput Illumina sequencing. Methodology/Principal Findings In a single run, more than 60 million sequencing reads were generated. De novo assembling was performed to generate a collection of 46,910 unigenes with mean length of 642 bp. Based on Blastx search with an E-value cut-off of 10−5, 22,581 unigenes showed significant similarities to known proteins from National Center for Biotechnology Information (NCBI) non-redundant (Nr) protein database. Of these annotated unigenes, 10,360, 6,937 and 13,894 were assigned to Gene Ontology (GO), Clusters of Orthologous Group (COG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively. A total of 5,926 unigenes were annotated with domain similarity derived functional information, of which 55 and 39 unigenes respectively encoding the insecticide resistance related enzymes, cytochrome P450 and carboxylesterase. Using the transcriptome data, 47 unigenes belonging to the typical “stress” genes of heat shock protein (Hsp) family were retrieved. Furthermore, 1,450 simple sequence repeats (SSRs) were detected; 3.09% of the unigenes contained SSRs. Large numbers of SSR primer pairs were designed and out of randomly verified primer pairs 80% were successfully yielded amplicons. Conclusions/Significance A large of putative R. leptotubula transcript sequences has been obtained from the deep sequencing, which extensively increases the comprehensive and integrated genomic resources of this pest. This large-scale transcriptome dataset will be an important information platform for promoting our investigation of the molecular mechanisms from various aspects in this species.
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26
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Poschmann G, Lendzian A, Uszkoreit J, Eisenacher M, Borght AV, Ramaekers FC, Meyer HE, Stühler K. A combination of two electrophoretical approaches for detailed proteome-based characterization of SCLC subtypes. Arch Physiol Biochem 2013; 119:114-25. [PMID: 23651173 DOI: 10.3109/13813455.2013.789529] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
CONTEXT Small cell lung cancers (SCLC) are heterogeneous and tumours differ in growth characteristics and treatment resistance. OBJECTIVE To get insight into the underlying protein profiles responsible for this heterogeneity, two subtypes of SCLC cells mutually differing in chemo resistance properties and growth characteristics are analysed. MATERIALS AND METHODS Two different electrophoresis approaches in combination with mass spectrometry were used to detect differences between the SCLC cell lines GLC1 and GLC1M13: IEF/SDS-PAGE as well as cetyltrimethylammonium bromide (CTAB)-SDS-PAGE. RESULTS Altogether 60 non redundant differentially expressed proteins were found of which 5 were verified by Western Blot analysis. DISCUSSION Most of these proteins identified are involved in processes of tumour progression. Therefore, these proteins are interesting candidates for further functional analysis. CONCLUSION Additional CTAB-SDS page is a complementary method to IEF-SDS page revealing a complete new subset of proteins differentially expressed between GLC1 and GLC1 M13 cells SCLC subtypes.
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MESH Headings
- Blotting, Western
- Cell Line, Tumor
- Cetrimonium
- Cetrimonium Compounds/chemistry
- Drug Resistance, Neoplasm
- Electrophoresis, Gel, Two-Dimensional/methods
- Electrophoresis, Polyacrylamide Gel/methods
- Gene Expression Profiling
- Gene Expression Regulation, Neoplastic
- Humans
- Image Processing, Computer-Assisted
- Isoelectric Focusing
- Lung Neoplasms/chemistry
- Lung Neoplasms/diagnosis
- Lung Neoplasms/genetics
- Lung Neoplasms/pathology
- Molecular Sequence Annotation
- Neoplasm Proteins/analysis
- Neoplasm Proteins/genetics
- Proteomics
- Small Cell Lung Carcinoma/chemistry
- Small Cell Lung Carcinoma/diagnosis
- Small Cell Lung Carcinoma/genetics
- Small Cell Lung Carcinoma/pathology
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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Affiliation(s)
- Gereon Poschmann
- Molecular Proteomics Laboratory, BMFZ, Universität Düsseldorf, Germany.
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27
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Chen H, Chou M, Wang X, Liu S, Zhang F, Wei G. Profiling of differentially expressed genes in roots of Robinia pseudoacacia during nodule development using suppressive subtractive hybridization. PLoS One 2013; 8:e63930. [PMID: 23776436 PMCID: PMC3679122 DOI: 10.1371/journal.pone.0063930] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2012] [Accepted: 04/09/2013] [Indexed: 11/23/2022] Open
Abstract
Background Legume-rhizobium symbiosis is a complex process that is regulated in the host plant cell through gene expression network. Many nodulin genes that are upregulated during different stages of nodulation have been identified in leguminous herbs. However, no nodulin genes in woody legume trees, such as black locust (Robinia pseudoacacia), have yet been reported. Methodology/Principal findings To identify the nodulin genes involved in R. pseudoacacia-Mesorhizobium amorphae CCNWGS0123 symbiosis, a suppressive subtractive hybridization approach was applied to reveal profiling of differentially expressed genes and two subtracted cDNA libraries each containing 600 clones were constructed. Then, 114 unigenes were identified from forward SSH library by differential screening and the putative functions of these translational products were classified into 13 categories. With a particular interest in regulatory genes, twenty-one upregulated genes encoding potential regulatory proteins were selected based on the result of reverse transcription-polymerase chain reaction (RT-PCR) analysis. They included nine putative transcription genes, eight putative post-translational regulator genes and four membrane protein genes. The expression patterns of these genes were further analyzed by quantitative RT-PCR at different stages of nodule development. Conclusions The data presented here offer the first insights into the molecular foundation underlying R. pseudoacacia–M. amorphae symbiosis. A number of regulatory genes screened in the present study revealed a high level of regulatory complexity (transcriptional, post-transcriptional, translational and post-translational) that is likely essential to develop symbiosis. In addition, the possible roles of these genes in black locust nodulation are discussed.
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Affiliation(s)
- Hongyan Chen
- State Key Laboratory of Crop Stress Biology in Arid Areas, College of Life Sciences, Northwest Agriculture & Forestry University, Yangling, Shaanxi, China
| | - Minxia Chou
- State Key Laboratory of Crop Stress Biology in Arid Areas, College of Life Sciences, Northwest Agriculture & Forestry University, Yangling, Shaanxi, China
| | - Xinye Wang
- State Key Laboratory of Crop Stress Biology in Arid Areas, College of Life Sciences, Northwest Agriculture & Forestry University, Yangling, Shaanxi, China
| | - Sisi Liu
- State Key Laboratory of Crop Stress Biology in Arid Areas, College of Life Sciences, Northwest Agriculture & Forestry University, Yangling, Shaanxi, China
| | - Feilong Zhang
- State Key Laboratory of Crop Stress Biology in Arid Areas, College of Life Sciences, Northwest Agriculture & Forestry University, Yangling, Shaanxi, China
| | - Gehong Wei
- State Key Laboratory of Crop Stress Biology in Arid Areas, College of Life Sciences, Northwest Agriculture & Forestry University, Yangling, Shaanxi, China
- * E-mail:
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28
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Jin Y, Zhang X, Lu D, Fu Z. Proteomic analysis of hepatic tissue in adult female zebrafish (Danio rerio) exposed to atrazine. ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY 2012; 62:127-134. [PMID: 21594674 DOI: 10.1007/s00244-011-9678-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/17/2010] [Accepted: 05/04/2011] [Indexed: 05/30/2023]
Abstract
Atrazine (ATZ), the most common herbicide, is a frequently observed contaminant in freshwater ecosystems. In the present study, two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization tandem time-of-flight-mass spectrometry, combined with histopathological analysis, were used to detect the hepatic damage in adult female zebrafish (Danio rerio) exposed to ATZ. More than 600 hepatic protein spots were detected in each gel with silver staining, and most of the proteins ranged from 20 to 70 kD and pH 4-9. Through comparison and analysis, 7 proteins were found to be upregulated>2-fold, whereas 6 protein spots were downregulated>2-fold after 10 and 1000 μg/l ATZ exposures for 14 days, which had caused histological effects in zebrafish livers. We found that these changed proteins were associated with a variety of cellular biological processes, such as response to oxidative stress, oncogenesis, etc. The results demonstrated that ATZ comprehensively influenced a variety of cellular and biological processes in zebrafish. The information presented in this study will be helpful in fully understanding the mechanism of the potential effects induced by ATZ in fish.
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Affiliation(s)
- Yuanxiang Jin
- College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou, 310032, China
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29
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Tomasello G, Sciumé C, Rappa F, Rodolico V, Zerilli M, Martorana A, Cicero G, De Luca R, Damiani P, Accardo FM, Romeo M, Farina F, Bonaventura G, Modica G, Zummo G, Conway de Macario E, Macario AJL, Cappello F. Hsp10, Hsp70, and Hsp90 immunohistochemical levels change in ulcerative colitis after therapy. Eur J Histochem 2011; 55:e38. [PMID: 22297444 PMCID: PMC3284240 DOI: 10.4081/ejh.2011.e38] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2011] [Revised: 10/17/2011] [Accepted: 10/17/2011] [Indexed: 01/11/2023] Open
Abstract
Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) characterized by damage of large bowel mucosa and frequent extra-intestinal autoimmune comorbidities. The role played in IBD pathogenesis by molecular chaperones known to interact with components of the immune system involved in inflammation is unclear. We previously demonstrated that mucosal Hsp60 decreases in UC patients treated with conventional therapies (mesalazine, probiotics), suggesting that this chaperonin could be a reliable biomarker useful for monitoring response to treatment, and that it might play a role in pathogenesis. In the present work we investigated three other heat shock protein/molecular chaperones: Hsp10, Hsp70, and Hsp90. We found that the levels of these proteins are increased in UC patients at the time of diagnosis and decrease after therapy, supporting the notion that these proteins deserve attention in the study of the mechanisms that promote the development and maintenance of IBD, and as biomarkers of this disease (e.g., to monitor response to treatment at the histological level).
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Affiliation(s)
- G Tomasello
- Dipartimento di Discipline Chirurgiche ed Oncologiche, Università di Palermo, Italy
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30
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Zhang X, Dai L, Wu Z, Jian J, Lu Y. Molecular cloning, mRNA expression, and characterization of heat shock protein 10 gene from humphead snapper Lutjanus sanguineus. Mar Genomics 2011; 4:143-50. [DOI: 10.1016/j.margen.2010.10.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2010] [Revised: 10/04/2010] [Accepted: 10/05/2010] [Indexed: 10/18/2022]
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31
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32
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Madrigal-Matute J, Martin-Ventura JL, Blanco-Colio LM, Egido J, Michel JB, Meilhac O. Heat-shock proteins in cardiovascular disease. Adv Clin Chem 2011; 54:1-43. [PMID: 21874755 DOI: 10.1016/b978-0-12-387025-4.00001-7] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Heat-shock proteins (HSPs) belong to a group of highly conserved families of proteins expressed by all cells and organisms and their expression may be constitutive or inducible. They are generally considered as protective molecules against different types of stress and have numerous intracellular functions. Secretion or release of HSPs has also been described, and potential roles for extracellular HSPs reported. HSP expression is modulated by different stimuli involved in all steps of atherogenesis including oxidative stress, proteolytic aggression, or inflammation. Also, antibodies to HSPs may be used to monitor the response to different types of stress able to induce changes in HSP levels. In the present review, we will focus on the potential implication of HSPs in atherogenesis and discuss the limitations to the use of HSPs and anti-HSPs as biomarkers of atherothrombosis. HSPs could also be considered as potential therapeutic targets to reinforce vascular defenses and delay or avoid clinical complications associated with atherothrombosis.
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Affiliation(s)
- Julio Madrigal-Matute
- Vascular Research Lab, IIS, Fundación Jiménez Díaz, Autónoma University, Av. Reyes Católicos 2, Madrid, Spain
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33
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Jia H, Halilou AI, Hu L, Cai W, Liu J, Huang B. Heat shock protein 10 (Hsp10) in immune-related diseases: one coin, two sides. INTERNATIONAL JOURNAL OF BIOCHEMISTRY AND MOLECULAR BIOLOGY 2010; 2:47-57. [PMID: 21969171 PMCID: PMC3180030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 12/14/2010] [Accepted: 12/22/2010] [Indexed: 05/31/2023]
Abstract
Heat shock protein 10 (Hsp10) in eukaryotes, originally identified as a mitochondrial chaperone, now is also known to be present in cytosol, cell surface, extracellular space and peripheral blood. Functionally besides participating in mitochondrial protein folding in association with Hsp60, Hsp10 appears to be related to pregnancy, cancer and autoimmune inhibition. Hsp10 can be released to peripheral blood at very early time point of pregnancy and given another name called early pregnancy factor (EPF), which seems to play a critical role in developing a pregnant niche. In malignant disorders, Hsp10 is usually abnormally expressed in the cytosol of malignant cells and further released to extracellular space, resulting in tumor-promoting effect from various aspects. Furthermore, distinct from other heat shock protein members, whose soluble form is recognized as danger signal by immune cells and triggers immune responses, Hsp10 after release, however, is designed to be an inhibitory signal by limiting immune response. This review discusses how Hsp10 participates in various physiological and pathological processes from basic protein molecule folding to pregnancy, cancer and autoimmune diseases, and emphasizes how important the location is for the function exertion of a molecule.
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Affiliation(s)
- Haibo Jia
- Department of Biology Science, College of Life Science and Technology
| | - Amadou I. Halilou
- Department of Biochemistry & Molecular Biology, Tongji Medical College; Huazhong University of Science & TechnologyWuhan 430030, The People's Republic of China
| | - Liang Hu
- Department of Biochemistry & Molecular Biology, Tongji Medical College; Huazhong University of Science & TechnologyWuhan 430030, The People's Republic of China
| | - Wenqian Cai
- Department of Biochemistry & Molecular Biology, Tongji Medical College; Huazhong University of Science & TechnologyWuhan 430030, The People's Republic of China
| | - Jing Liu
- Department of Biochemistry & Molecular Biology, Tongji Medical College; Huazhong University of Science & TechnologyWuhan 430030, The People's Republic of China
| | - Bo Huang
- Department of Biochemistry & Molecular Biology, Tongji Medical College; Huazhong University of Science & TechnologyWuhan 430030, The People's Republic of China
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34
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Rodolico V, Tomasello G, Zerilli M, Martorana A, Pitruzzella A, Marino Gammazza A, David S, Zummo G, Damiani P, Accomando S, Conway de Macario E, Macario AJL, Cappello F. Hsp60 and Hsp10 increase in colon mucosa of Crohn’s disease and ulcerative colitis. Cell Stress Chaperones 2010; 15:877-84. [PMID: 20390473 PMCID: PMC3024080 DOI: 10.1007/s12192-010-0196-8] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2010] [Revised: 03/25/2010] [Accepted: 03/26/2010] [Indexed: 12/13/2022] Open
Abstract
The purpose of this work was to determine in colon mucosa of Crohn’s disease (CD) and ulcerative colitis (UC) in relapse: a) the levels of the chaperonins Hsp60 and Hsp10; b) the quantity of inflammatory cells; and c) if the levels of chaperonins parallel those of inflammation cells. Twenty cases of CD and UC and twenty normal controls (NC) were studied using immunohistochemistry, Western blotting and immunofluorescence. Immunohistochemically, Hsp60 and Hsp10 were increased in both inflammatory bowel diseases (IBD) compared to NC. These results were confirmed by Western blotting. Hsp60 and Hsp10 occurred in the cytoplasm of epithelial cells in CD and UC but not in NC. Hsp60 and Hsp10 co-localised to epithelial cells of mucosal glands but not always in connective tissue cells of lamina propria, where only Hsp60 or, less often, Hsp10 was found. Cells typical of inflammation were significantly more abundant in CD and UC than in NC. Since chaperonins are key factors in the activation of the immune system leading to inflammation, we propose that they play a central role in the pathogenesis of the two diseases, which, consequently, ought to be studied as chaperonopathies.
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Affiliation(s)
- Vito Rodolico
- Dipartimento di Patologia Umana, Università degli Studi di Palermo, Palermo, Italy
| | - Giovanni Tomasello
- Dipartimento di Chirurgia Generale, d’Urgenza e Trapianti d’Organo, Università degli Studi di Palermo, Palermo, Italy
| | - Monica Zerilli
- Dipartimento di Patologia Umana, Università degli Studi di Palermo, Palermo, Italy
| | - Anna Martorana
- Dipartimento di Patologia Umana, Università degli Studi di Palermo, Palermo, Italy
| | - Alessandro Pitruzzella
- Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Università degli Studi di Palermo, Sezione di Anatomia Umana, via del Vespro 129, 90127 Palermo, Italy
| | - Antonella Marino Gammazza
- Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Università degli Studi di Palermo, Sezione di Anatomia Umana, via del Vespro 129, 90127 Palermo, Italy
| | - Sabrina David
- Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Università degli Studi di Palermo, Sezione di Anatomia Umana, via del Vespro 129, 90127 Palermo, Italy
| | - Giovanni Zummo
- Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Università degli Studi di Palermo, Sezione di Anatomia Umana, via del Vespro 129, 90127 Palermo, Italy
| | - Provvidenza Damiani
- Dipartimento di Medicina Interna, Malattie Cardiovascolari e Nefrourologiche, Università degli Studi di Palermo, Palermo, Italy
| | - Salvatore Accomando
- Dipartimento Materno-Infantile, Università degli Studi di Palermo, Palermo, Italy
| | | | | | - Francesco Cappello
- Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Università degli Studi di Palermo, Sezione di Anatomia Umana, via del Vespro 129, 90127 Palermo, Italy
- Istituto Euro-Mediterraneo di Scienza e Tecnologia (IEMEST), Palermo, Italy
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35
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He Y, Shang X, Sun J, Zhang L, Zhao W, Tian Y, Cheng H, Zhou R. Gonadal apoptosis during sex reversal of the rice field eel: implications for an evolutionarily conserved role of the molecular chaperone heat shock protein 10. JOURNAL OF EXPERIMENTAL ZOOLOGY PART B-MOLECULAR AND DEVELOPMENTAL EVOLUTION 2010; 314:257-66. [PMID: 20035552 DOI: 10.1002/jez.b.21333] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Role of apoptosis in gonadal transformation of the rice field eel remains unknown. Here we report characterization of apoptotic pattern of testis, ovary, and ovotestis of the rice field eel, a vertebrate with natural sex reversal characteristic. DNA laddering assay showed typical ladder with step around 200 bp in the gonads, especially in testis. Terminal transferase dUTP nick end labeling on gonads indicated obvious apoptotic signals in the seminiferous tubules. Western blot analysis revealed that pro-apoptotic genes, Caspase 9 and p53, were upregulated and anti-apoptotic factor Bcl2 was downregulated in testis compared with both ovary and ovotestis. These data indicated that sex reversal process is accompanied by gonadal apoptosis with the highest proportion of cell death in the testis. Furthermore, we identified the Hsp10 by differentially screening of testis, ovary, and ovotestis using microarray technique, which is evolutionarily conserved and differentially expressed during gonadal transformation. Downregulation of Hsp10 is consistent with high apoptosis during the gonadal transformation. Flow cytometry assay confirmed that Hsp10 inhibits the apoptosis in male gonadal cells. Moreover, upregulation and mis-localization at sub-cellular level of the HSP10 together with its partner HSP60 is associated with tumorigenesis in human testis. These results suggest that downregulation of Hsp10 would be one of the main causes of apoptosis in testis, overexpression of Hsp10 suppresses apoptosis, and potentially results in testis tumorigenesis, which provide clues for understanding the mechanisms of germ cell apoptosis. Development of Hsp10 as a diagnostic marker or even treatment target will be promising in testis cancer diagnosis and therapy.
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Affiliation(s)
- Yan He
- Department of Genetics and Center for Developmental Biology, College of Life Science, Wuhan University, Wuhan, China
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36
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Kayani AC, Close GL, Dillmann WH, Mestril R, Jackson MJ, McArdle A. Overexpression of HSP10 in skeletal muscle of transgenic mice prevents the age-related fall in maximum tetanic force generation and muscle Cross-Sectional Area. Am J Physiol Regul Integr Comp Physiol 2010; 299:R268-76. [PMID: 20410481 DOI: 10.1152/ajpregu.00334.2009] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Skeletal muscle atrophy and weakness are major contributors to frailty and impact significantly on quality of life of older people. Muscle aging is characterized by a loss of maximum tetanic force (P(o)) generation, primarily due to muscle atrophy, to which mitochondrial dysfunction is hypothesized to contribute. We hypothesized that lifelong overexpression of the mitochondrial heat shock protein (HSP) HSP10 in muscle of mice would protect against development of these deficits. P(o) generation by extensor digitorum longus muscles of adult and old wild-type and HSP10-overexpressing mice was determined in situ. Muscles were subjected to damaging lengthening contractions, and force generation was remeasured at 3 h or 28 days to examine susceptibility to, and recovery from, damage, respectively. Muscles of old wild-type mice had a 23% deficit in P(o) generation and a 10% deficit in muscle cross-sectional area compared with muscles of adult wild-type mice. Overexpression of HSP10 prevented this age-related fall in P(o) generation and reduction in cross-sectional area observed in muscles of old wild-type mice. Additionally, overexpression of HSP10 protected against contraction-induced damage independent of age but did not improve recovery if damage occurred. Preservation of muscle force generation and CSA by HSP10 overexpression was associated with protection against the age-related accumulation of protein carbonyls. Data demonstrate that development of age-related muscle weakness may not be inevitable and show, for the first time, that lifelong overexpression of an HSP prevents the age-related loss of P(o) generation. These findings support the hypothesis that mitochondrial dysfunction is involved in the development of age-related muscle deficits.
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Affiliation(s)
- Anna C Kayani
- Pathophysiology Research Unit, School of Clinical Sciences, University of Liverpool, Liverpool, United Kingdom
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37
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Corrao S, Campanella C, Anzalone R, Farina F, Zummo G, Conway de Macario E, Macario AJL, Cappello F, La Rocca G. Human Hsp10 and Early Pregnancy Factor (EPF) and their relationship and involvement in cancer and immunity: current knowledge and perspectives. Life Sci 2009; 86:145-52. [PMID: 19913561 DOI: 10.1016/j.lfs.2009.11.004] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2009] [Revised: 10/29/2009] [Accepted: 11/05/2009] [Indexed: 02/02/2023]
Abstract
This article is about Hsp10 and its intracellular and extracellular forms focusing on the relationship of the latter with Early Pregnancy Factor and on their roles in cancer and immunity. Cellular physiology and survival are finely regulated and depend on the correct functioning of the entire set of proteins. Misfolded or unfolded proteins can cause deleterious effects and even cell death. The chaperonins Hsp10 and Hsp60 act together inside the mitochondria to assist protein folding. Recent studies demonstrated that these proteins have other roles inside and outside the cell, either together or independently of each other. For example, Hsp10 was found increased in the cytosol of different tumors (although in other tumors it was found decreased). Moreover, Hsp10 localizes extracellularly during pregnancy and is often indicated as Early Pregnancy Factor (EPF), which is released during the first stages of gestation and is involved in the establishment of pregnancy. Various reports show that extracellular Hsp10 and EPF modulate certain aspects of the immune response with anti-inflammatory effects in patients with autoimmune conditions improving clinically after treatment with recombinant Hsp10. Moreover, Hsp10 and EPF are involved in embryonic development, acting as a growth factor, and in cell proliferation/differentiation mechanisms. Therefore, it becomes evident that Hsp10 is not only a co-chaperonin, but an active player in its own right in various cellular functions. In this article, we present an overview of various aspects of Hsp10 and EPF as they participate in physiological and pathological processes such as the antitumor response and autoimmune diseases.
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Affiliation(s)
- Simona Corrao
- Dipartimento di Medicina Sperimentale, Università degli Studi di Palermo, Via del Vespro 129, 90127, Palermo, Italy.
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Cadmium and mitochondria. Mitochondrion 2009; 9:377-84. [PMID: 19706341 DOI: 10.1016/j.mito.2009.08.009] [Citation(s) in RCA: 148] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2009] [Revised: 08/18/2009] [Accepted: 08/19/2009] [Indexed: 11/20/2022]
Abstract
The heavy metal cadmium (Cd) a pollutant associated with several modern industrial processes, is absorbed in significant quantities from cigarette smoke, water, food and air contaminations. It is known to have numerous undesirable effects on health in both experimental animals and humans, targeting kidney, liver and vascular system. The molecular mechanism accounting for most of the biological effects of Cd are not well-understood and the toxicity targets are largely unidentified. The present review focuses on important recent advances about the effects of cadmium on mitochondria of mammalian cells. Mitochondria are the proverbial powerhouses of the cell, running the fundamental biochemical processes that produce energy from nutrients using oxygen. They are among the key intracellular targets for different stressors including Cd. This review provides new additional informations on the cellular and molecular aspects of the interaction between Cd and cells, emphasizing alterations of mitochondria as important events in Cd cytotoxicity, thus representing an important basis for understanding the mechanisms of cadmium effect on the cells.
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Henderson B, Henderson S. Unfolding the relationship between secreted molecular chaperones and macrophage activation states. Cell Stress Chaperones 2009; 14:329-41. [PMID: 18958583 PMCID: PMC2728268 DOI: 10.1007/s12192-008-0087-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2008] [Revised: 10/01/2008] [Accepted: 10/02/2008] [Indexed: 02/07/2023] Open
Abstract
Over the last 20 years, it has emerged that many molecular chaperones and protein-folding catalysts are secreted from cells and function, somewhat in the manner of cytokines, as pleiotropic signals for a variety of cells, with much attention being focused on the macrophage. During the last decade, it has become clear that macrophages respond to bacterial, protozoal, parasitic and host signals to generate phenotypically distinct states of activation. These activation states have been termed 'classical' and 'alternative' and represent not a simple bifurcation in response to external signals but a range of cellular phenotypes. From an examination of the literature, the hypothesis is propounded that mammalian molecular chaperones are able to induce a wide variety of alternative macrophage activation states, and this may be a system for relating cellular or tissue stress to appropriate macrophage responses to restore homeostatic equilibrium.
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Affiliation(s)
- Brian Henderson
- Division of Microbial Diseases, UCL Eastman Dental Institute, University College London, London, UK.
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40
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Fan L, Fan L, Ling J, Ma X, Cui YG, Liu JY. Involvement of HSP10 during the ovarian follicular development of polycystic ovary syndrome: Study in both human ovaries and cultured mouse follicles. Gynecol Endocrinol 2009; 25:392-7. [PMID: 19903031 DOI: 10.1080/09513590902730796] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Abstract
OBJECTIVE To study the possible roles of HSP10 in the follicular development. METHODS In this study, we examined the expression of HSP10 during the follicular development in human ovaries and cultured mouse follicles as well as its functional relevance with PCOS. Ovary tissues from normal adults (n = 3) were obtained with consents. Mouse early antral follicles (diameter: 220-250 mum) were cultured for 3 days in vitro. Western Blot and immunohistochemistry were used to determine the HSP10 expression and localisation during follicular development in vivo and in vitro. RESULTS HSP10 protein was detected only in oocytes from human preantral follicles, whereas in antral follicles, it was localised in oocytes, granulosa cells, theca cells and stroma cells. Furthermore, in cultured mouse antral follicles, a similar trend of HSP10 expression during follicle development was observed. CONCLUSION HSP10 expression was increased as larger area and higher level of density during follicular development both in human and mouse follicles cultured in vitro. Our previous studies showed that HSP10 was highly expressed in normal ovaries compared with those from PCOS. The mouse early antral follicle culture approach may help to understand the role of HSP10 in pathophysiological development of PCOS.
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Affiliation(s)
- Lu Fan
- Jiangsu Province Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China
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41
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Effects of cadmium chloride on some mitochondria-related activity and gene expression of human MDA-MB231 breast tumor cells. J Inorg Biochem 2008; 102:1668-76. [DOI: 10.1016/j.jinorgbio.2008.04.002] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2007] [Revised: 04/14/2008] [Accepted: 04/15/2008] [Indexed: 11/18/2022]
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Walsh A, Whelan D, Bielanowicz A, Skinner B, Aitken RJ, O'Bryan MK, Nixon B. Identification of the Molecular Chaperone, Heat Shock Protein 1 (Chaperonin 10), in the Reproductive Tract and in Capacitating Spermatozoa in the Male Mouse1. Biol Reprod 2008; 78:983-93. [DOI: 10.1095/biolreprod.107.066860] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
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43
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Chaperonin 10 as a putative modulator of multiple Toll-like receptors for the treatment of inflammatory diseases. Expert Opin Ther Pat 2007. [DOI: 10.1517/13543776.17.10.1299] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Abstract
The stress response, stress proteins, heat-shock genes and proteins, molecular chaperone genes and proteins, and a number of closely related molecules and cellular processes have been studied over the last few decades. A huge amount of information has accumulated that is scattered in printed and electronic literature and databases. Most of this information constitutes the subject matter of the science of chaperonology. More recently, the concept of chaperone pathology, sick chaperones, has evolved since various pathological conditions have been identified in which defective chaperones play an etiologic role. These conditions are the chaperonopathies. Recent findings on chaperonopathies are briefly discussed in this article. Chaperonopathies occur at all ages; as a rule the genetic cases have an early clinical onset while the acquired chaperonopathies become manifest in the elderly and/or in association with other diseases. Other fields of chaperonology, which will most likely be expanded in the near future, are the study of extracellular chaperones, chaperone networks, the therapeutic use of chaperones (i.e., chaperonotherapy) to manage chaperonopathies and to improve cell performance in the face of stress, the evaluation of chaperones as diagnostic markers and as prognostic indicators, and the development of antichaperone agents to suppress chaperone-gene expression or inhibit chaperone function when chaperones contribute to disease rather than the opposite.
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Affiliation(s)
- Alberto J L Macario
- University of Maryland Biotechnology Institute, Center of Marine Biotechnology, 701 E. Pratt Street, Baltimore, MD 21202, USA.
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Macario AJL, Conway de Macario E. Chaperonopathies and chaperonotherapy. FEBS Lett 2007; 581:3681-8. [PMID: 17475257 DOI: 10.1016/j.febslet.2007.04.030] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2007] [Revised: 04/05/2007] [Accepted: 04/15/2007] [Indexed: 11/23/2022]
Abstract
The study of molecular chaperones (genetics, structure, location, physiology, pathology, and therapeutics) has developed into a science with specific objectives, methods, and hypotheses, a discipline we called chaperonology. Subdisciplines of chaperonology include the study of pathological chaperones (chaperonopathies) and the analysis of their genes in sequenced genomes (chaperonomics). Chaperonopathies are pathological conditions in which one type of chaperone is deficient due to a genetic or acquired defect that modifies the chaperone's structure and/or makes the chaperone unavailable for functioning when needed. Experimental and clinical data show that chaperones and their genes can be used for treating various pathological conditions, thus justifying the development of chaperonotherapy. We discuss recent work showing that chaperonotherapy is on solid foundations: the data demonstrate that molecular chaperones counteract pathogenetic mechanisms in disease and during stress.
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Affiliation(s)
- Alberto J L Macario
- University of Maryland Biotechnology Institute (UMBI), Columbus Center, 701 E. Pratt Street, Baltimore, MD 21202, USA.
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