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Verma N, Chouhan D, Meghana A, Tiwari V. Heat shock proteins in chronic pain: From molecular chaperones to pain modulators. Neuropharmacology 2025; 266:110263. [PMID: 39667433 DOI: 10.1016/j.neuropharm.2024.110263] [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] [Received: 09/22/2024] [Revised: 11/25/2024] [Accepted: 12/08/2024] [Indexed: 12/14/2024]
Abstract
Chronic pain is the most prevalent and complex clinical disorder,affecting approximately 30% of people globally. Various intricate alterations in nociceptive pathways responsible for chronic pain are linked to long-term tissue damage or injury to the peripheral or central nervous systems. These include remolding in the phenotype of cells and fluctuations in the expression of proteins such as ion channels, neurotransmitters, and receptors. Heat shock proteins are important molecular chaperone proteins in cell responses to stress, including inflammation, neurodegeneration, and pain signaling. They play a key role in activating glial and endothelial cells and in the production of inflammatory mediators and excitatory amino acids in both peripheral and central nervous systems. In particular, they contribute to central sensitization and hyperactivation within the dorsal horn of the spinal cord. The expression of some HSPs plays a remarkable role in upregulating pain response by acting as scavengers of ROS, controlling inflammatory cytokines. Different HSPs act by different mechanisms and several important pathways have been implicated in targeting HSPs for the treatment of neuropathic pain including p38-mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinases (ERKs), brain-derived neurotrophic factors (BDNF). We summarize the role of HSPs in various preclinical and clinical studies and the crosstalk of HSPs with various nociceptors and other pain models. We also highlighted some artificial intelligence tools and machine learning-assisted drug discovery methods for rapid screening of HSPs in various diseases. Focusing on HSPs could lead to the development of new therapeutics that modulate pain responses and enhance our understanding of pain in various pathological conditions and neurological disorders.
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Affiliation(s)
- Nivedita Verma
- Neuroscience and Pain Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, Uttar Pradesh, India
| | - Deepak Chouhan
- Neuroscience and Pain Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, Uttar Pradesh, India
| | - Allani Meghana
- Neuroscience and Pain Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, Uttar Pradesh, India
| | - Vinod Tiwari
- Neuroscience and Pain Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, Uttar Pradesh, India.
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El-Hussien M, Abdelhamid B, Elbadawy H, El-Hennawy H, Ahmed M. Performance Enhancement for B5G/6G Networks Based on Space Time Coding Schemes Assisted by Intelligent Reflecting Surfaces with Higher Modulation Orders. SENSORS (BASEL, SWITZERLAND) 2024; 24:6169. [PMID: 39409209 PMCID: PMC11478492 DOI: 10.3390/s24196169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 08/20/2024] [Accepted: 08/26/2024] [Indexed: 10/20/2024]
Abstract
Intelligent Reflecting Surfaces (IRS) and Multiple-Input Single-Output (MISO) technologies are essential in the fifth generation (5G) networks and beyond. IRS optimizes the signal propagation and the coverage and is a viable approach to address the issues caused by fading channels that limits the spectral efficiency, while MIMO enhances data rates, reliability, and spectral efficiency by using multiple antennas at both transmitter and receiver ends. This paper proposes an IRS-assisted MISO system using the Orthogonal Space-Time Block Code (OSTBC) scheme to enhance the channel reliability and reduce the Bit Error Rate (BER) in wireless communication systems. The proposed system exploits the benefits from the transmit diversity gain of the OSTBC scheme as well as from the bit energy to noise power spectral density (Eb/No) improvement of the IRS technology. The presented work explores these combined technologies across different modulation schemes. The obtained results outperform the similar previously published works by considering higher-order modulation schemes as well as the deployment of rate ¾ OSTBC-assisted IRS. Moreover, the obtained results demonstrate that the integration of OSTBC with IRS can yield significant performance improvements in terms of Eb/No by 7 dB and 13 dB when using 16 reflecting elements and 64 reflecting elements, respectively.
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Affiliation(s)
- Mariam El-Hussien
- Electronics and Communications Department, Faculty of Engineering Science and Arts, Misr International University, Cairo 11828, Egypt;
- Electronics and Communications Department, Faculty of Engineering, Ain Shams University, Cairo 11517, Egypt; (B.A.); (H.E.-H.)
| | - Bassant Abdelhamid
- Electronics and Communications Department, Faculty of Engineering, Ain Shams University, Cairo 11517, Egypt; (B.A.); (H.E.-H.)
| | - Hesham Elbadawy
- Network Planning Department, National Telecommunications Institute, Cairo 11768, Egypt;
| | - Hadia El-Hennawy
- Electronics and Communications Department, Faculty of Engineering, Ain Shams University, Cairo 11517, Egypt; (B.A.); (H.E.-H.)
| | - Mehaseb Ahmed
- Electronics and Communications Department, Faculty of Engineering Science and Arts, Misr International University, Cairo 11828, Egypt;
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Yadav M, Chaudhary PP, Ratley G, D’Souza B, Kaur M, Ganesan S, Kabat J, Myles IA. TRPA1 Influences Staphylococcus aureus Skin Infection in Mice and Associates with HIF-1a and MAPK Pathway Modulation. Int J Mol Sci 2024; 25:9933. [PMID: 39337422 PMCID: PMC11432213 DOI: 10.3390/ijms25189933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 09/05/2024] [Accepted: 09/10/2024] [Indexed: 09/30/2024] Open
Abstract
Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a major public health burden. Emerging antibiotic resistance has heightened the need for new treatment approaches for MRSA infection such as developing novel antimicrobial agents and enhancing the host's defense response. The thermo-ion channels Transient Receptor Potential (TRP-) A1 and V1 have been identified as modulators of S. aureus quorum sensing in cell culture models. However, their effects on in vivo infection control are unknown. In this study, we investigated the therapeutic effect of natural TRP ion channel inhibitors on MRSA skin infection in mice. While deletion of TRPV1 did not affect lesion size or inflammatory markers, TRPA1-/- mice demonstrated significantly reduced infection severity and abscess size. Treatment with natural inhibitors of TRPA1 with or without blockade of TRPV1 also reduced abscess size. Tissue transcriptomic data coupled with immunohistochemistry revealed that TRPA1 inhibition impacted heat shock protein expression (HSP), modulated the HIF-1a and MAPK pathways, and reduced IL4 expression. Additionally, metabolomics data showed an impact on purine and glycosaminoglycan pathways. Multi-omic integration of transcriptomic and metabolic data revealed that diacylglycerol metabolism was the likely bridge between metabolic and immunological impacts. Our findings suggest that TRPA1 antagonism could provide a promising and cost-effective therapeutic approach for reducing the severity of MRSA infection, and presents a novel underlying molecular mechanism.
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Affiliation(s)
- Manoj Yadav
- Epithelial Therapeutic Unit, National Institute of Allergy, and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA; (P.P.C.); (G.R.); (B.D.); (M.K.); (I.A.M.)
| | - Prem Prashant Chaudhary
- Epithelial Therapeutic Unit, National Institute of Allergy, and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA; (P.P.C.); (G.R.); (B.D.); (M.K.); (I.A.M.)
| | - Grace Ratley
- Epithelial Therapeutic Unit, National Institute of Allergy, and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA; (P.P.C.); (G.R.); (B.D.); (M.K.); (I.A.M.)
| | - Brandon D’Souza
- Epithelial Therapeutic Unit, National Institute of Allergy, and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA; (P.P.C.); (G.R.); (B.D.); (M.K.); (I.A.M.)
| | - Mahaldeep Kaur
- Epithelial Therapeutic Unit, National Institute of Allergy, and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA; (P.P.C.); (G.R.); (B.D.); (M.K.); (I.A.M.)
| | - Sundar Ganesan
- Biological Imaging Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; (S.G.); (J.K.)
| | - Juraj Kabat
- Biological Imaging Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; (S.G.); (J.K.)
| | - Ian A. Myles
- Epithelial Therapeutic Unit, National Institute of Allergy, and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA; (P.P.C.); (G.R.); (B.D.); (M.K.); (I.A.M.)
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Premji TP, Dash BS, Das S, Chen JP. Functionalized Nanomaterials for Inhibiting ATP-Dependent Heat Shock Proteins in Cancer Photothermal/Photodynamic Therapy and Combination Therapy. NANOMATERIALS (BASEL, SWITZERLAND) 2024; 14:112. [PMID: 38202567 PMCID: PMC10780407 DOI: 10.3390/nano14010112] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 12/20/2023] [Accepted: 12/27/2023] [Indexed: 01/12/2024]
Abstract
Phototherapies induced by photoactive nanomaterials have inspired and accentuated the importance of nanomedicine in cancer therapy in recent years. During these light-activated cancer therapies, a nanoagent can produce heat and cytotoxic reactive oxygen species by absorption of light energy for photothermal therapy (PTT) and photodynamic therapy (PDT). However, PTT is limited by the self-protective nature of cells, with upregulated production of heat shock proteins (HSP) under mild hyperthermia, which also influences PDT. To reduce HSP production in cancer cells and to enhance PTT/PDT, small HSP inhibitors that can competitively bind at the ATP-binding site of an HSP could be employed. Alternatively, reducing intracellular glucose concentration can also decrease ATP production from the metabolic pathways and downregulate HSP production from glucose deprivation. Other than reversing the thermal resistance of cancer cells for mild-temperature PTT, an HSP inhibitor can also be integrated into functionalized nanomaterials to alleviate tumor hypoxia and enhance the efficacy of PDT. Furthermore, the co-delivery of a small-molecule drug for direct HSP inhibition and a chemotherapeutic drug can integrate enhanced PTT/PDT with chemotherapy (CT). On the other hand, delivering a glucose-deprivation agent like glucose oxidase (GOx) can indirectly inhibit HSP and boost the efficacy of PTT/PDT while combining these therapies with cancer starvation therapy (ST). In this review, we intend to discuss different nanomaterial-based approaches that can inhibit HSP production via ATP regulation and their uses in PTT/PDT and cancer combination therapy such as CT and ST.
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Affiliation(s)
- Thejas P. Premji
- Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan; (T.P.P.); (B.S.D.); (S.D.)
| | - Banendu Sunder Dash
- Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan; (T.P.P.); (B.S.D.); (S.D.)
| | - Suprava Das
- Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan; (T.P.P.); (B.S.D.); (S.D.)
| | - Jyh-Ping Chen
- Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan; (T.P.P.); (B.S.D.); (S.D.)
- Craniofacial Research Center, Chang Gung Memorial Hospital at Linkou, Kwei-San, Taoyuan 33305, Taiwan
- Department of Neurosurgery, Chang Gung Memorial Hospital at Linkou, Kwei-San, Taoyuan 33305, Taiwan
- Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33305, Taiwan
- Department of Materials Engineering, Ming Chi University of Technology, Tai-Shan, New Taipei City 24301, Taiwan
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Transient receptor potential (TRP) channels in the Manila clam (Ruditapes philippinarum): Characterization and expression patterns of the TRP gene family under heat stress in Manila clams based on genome-wide identification. Gene 2023; 854:147112. [PMID: 36513188 DOI: 10.1016/j.gene.2022.147112] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Revised: 11/25/2022] [Accepted: 12/06/2022] [Indexed: 12/14/2022]
Abstract
In this study, we identified a total of 40 transient receptor potential genes (RpTRP) in Manila clam by genome-wide identification and classified them into four categories (TRPV, TRPA, TRPM, TRPC) based on gene structure and subfamily relationships. The protein length of RpTRP genes ranges from 281 amino acids to 1601 amino acids. Molecular weight and theoretical PI values range from 182.82 kDa to 32.43 kDa, respectively, with PI values between 5.17 and 9.25. By comparing the expression profiles of TRP genes during heat stress in Manila clams at different latitudes, we found that most genes in the TRP gene family were up-regulated in expression during heat challenge. Therefore, we determined that TRP genes have an important role in the heat stress of Manila clams. This work provides a basis for further studies on the molecular mechanisms of TRP-mediated heat tolerance in Manila clam and for explaining differences in heat tolerance in Manila clam at different latitudes through key differential TRP genes at the molecular level.
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de Alba G, López-Olmeda JF, Sánchez-Vázquez FJ. Rearing temperature conditions (constant vs. thermocycle) affect daily rhythms of thermal tolerance and sensing in zebrafish. J Therm Biol 2021; 97:102880. [PMID: 33863444 DOI: 10.1016/j.jtherbio.2021.102880] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 01/22/2021] [Accepted: 02/13/2021] [Indexed: 11/25/2022]
Abstract
In the wild, the environment does not remain constant, but periodically oscillates so that temperature rises in the daytime and drops at night, which generates a daily thermocycle. The effects of thermocycles on thermal tolerance have been previously described in fish. However, the impact of thermocycles on daytime-dependent thermal responses and daily rhythms of temperature tolerance and sensing expression mechanisms remain poorly understood. This study investigates the effects of two rearing conditions: constant (26 °C, C) versus a daily thermocycle (28 °C in the daytime; 24 °C at night, T) on the thermal tolerance response in zebrafish. Thermal tolerance (mortality) was assessed in 4dpf (days post fertilization) zebrafish larvae after acute heat shock (39 °C for 1 h) at two time points: middle of the light phase (ML) or middle of the dark phase (MD). Thermal stress responses were evaluated in adult zebrafish after a 37 °C challenge for 1 h at ML or MD to examine the expression of the heat-shock protein (HSP) (hsp70, hsp90ab1, grp94, hsp90aa1, hspb1, hsp47, cirbp) and transient receptor potential (TRP) channels (trpv4, trpm4a, trpm2, trpa1b) in the brain. Finally, the daily rhythms of gene expression of HSPs and TRPs were measured every 4 h for 24 h. The results revealed the larval mortality rates and the expression induction of most HSPs in adult zebrafish brain reached the highest values in fish reared under constant temperature and subjected to thermal shock at MD. The expression of most HSPs and TRPs was mainly synchronized to the light/dark (LD) cycle, regardless of the temperature regime. Most HSPs involved in hyperthermic challenges displayed diurnal rhythms with their acrophases in phase with warm-sensing thermoTRPs acrophases. The cold-sensing trpa1b peaked in the second half of the light period and slightly shifted toward the dark phase anticipating the acrophase of cirpb, which is involved in hypothermic challenges. These findings indicated that: a) thermal shocks are best tolerated in the daytime; b) the implementation of daily thermocycles during larval development reduces mortality and stress-cellular expression of HSPs to an acute thermal stress at MD; c) daily rhythms need to be considered when discussing physiological responses of thermal sensing and thermotolerance in zebrafish.
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Affiliation(s)
- Gonzalo de Alba
- Department of Physiology, Faculty of Biology, University of Murcia, 30100, Murcia, Spain
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Wang G, Wang X, Gao Q, Zhou M, Wang N. Effects of Heating-Conduction Dry Needling Therapy on Rats with Chronic Myofascial Pain Syndrome. J Manipulative Physiol Ther 2020; 43:506-514. [PMID: 32928569 DOI: 10.1016/j.jmpt.2019.05.008] [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] [Received: 10/12/2018] [Revised: 04/11/2019] [Accepted: 05/02/2019] [Indexed: 11/19/2022]
Abstract
OBJECTIVE This study aimed to investigate the effect of dry needling (DN) with 44°C heating on the pressure pain threshold (PPT) of rats with chronic myofascial pain syndrome (MPS) by regulating the transient receptor potential V1 channel. METHODS A total of 80 rats were divided into 5 groups: A, B, C, D, and E (16 in each group). The rats in Group A recovered naturally, while those in other groups received the DN treatment. The needles were heated to 40°C for the rats in Groups B and E and 44°C for the rats in Groups C and D. In addition, both Groups D and E received local capsaicin injection. PPTs of the gastrocnemius muscle and tolerance time of the plantar hot plate were measured before modeling, 1 day before the intervention, 24 hours after the intervention, and 7 days after the intervention. RESULTS PPTs of the gastrocnemius muscle for rats with MPS increased 7 days after DN and heating to 40°C. For the rats receiving DN at 44°C heating, PPTs increased 24 hours and 7 days after the intervention. Further, 44°C heating and capsaicin injection improved PPT. DN and 40°C heating followed by capsaicin injection improved PPT. CONCLUSION DN and 44°C heating had therapeutic effects on rats with MPS at 24 hours and at 7 days after the intervention. DN and 40°C heating had therapeutic effects 7 days after the intervention. DN and 44°C heating might exert therapeutic effects by regulating the transient receptor potential V1 channel.
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Affiliation(s)
- Gang Wang
- Department of Rehabilitation Medicine, The Chinese PLA General Hospital, Beijing, China
| | - Xinglin Wang
- Department of Rehabilitation Medicine, The Chinese PLA General Hospital, Beijing, China.
| | - Qian Gao
- Department of Rehabilitation Medicine, The Chinese PLA General Hospital, Beijing, China
| | - Ming Zhou
- Department of Rehabilitation Medicine, The Chinese PLA General Hospital, Beijing, China
| | - Ning Wang
- Department of Rehabilitation Medicine, The Chinese PLA General Hospital, Beijing, China
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Kominami K, Noda K, Takahashi N, Izumi T, Yonezawa K. Cardiovascular reactions for whole-body thermal therapy with a hot pack and Waon therapy. Int J Hyperthermia 2020; 37:184-191. [DOI: 10.1080/02656736.2020.1723719] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Affiliation(s)
- Kazuyuki Kominami
- Cardiac Rehabilitation Center, Sapporo Ryokuai Hospital, Sapporo, Japan
| | - Kazuki Noda
- Department of Rehabilitation, National Hospital Organization Hakodate Hospital, Hakodate, Japan
| | - Naoaki Takahashi
- Graduate School of Rehabilitation Sciences, Health Sciences University of Hokkaido, Tobetsu, Japan
| | - Tadashi Izumi
- Graduate School of Rehabilitation Sciences, Health Sciences University of Hokkaido, Tobetsu, Japan
| | - Kazuya Yonezawa
- Department of Clinical Research, National Hospital Organization Hakodate Hospital, Hakodate, Japan
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Lüling R, John H, Gudermann T, Thiermann H, Mückter H, Popp T, Steinritz D. Transient Receptor Potential Channel A1 (TRPA1) Regulates Sulfur Mustard-Induced Expression of Heat Shock 70 kDa Protein 6 ( HSPA6) In Vitro. Cells 2018; 7:cells7090126. [PMID: 30200301 PMCID: PMC6162519 DOI: 10.3390/cells7090126] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Revised: 08/23/2018] [Accepted: 08/28/2018] [Indexed: 12/15/2022] Open
Abstract
The chemosensory transient receptor potential ankyrin 1 (TRPA1) ion channel perceives different sensory stimuli. It also interacts with reactive exogenous compounds including the chemical warfare agent sulfur mustard (SM). Activation of TRPA1 by SM results in elevation of intracellular calcium levels but the cellular consequences are not understood so far. In the present study we analyzed SM-induced and TRPA1-mediated effects in human TRPA1-overexpressing HEK cells (HEKA1) and human lung epithelial cells (A549) that endogenously exhibit TRPA1. The specific TRPA1 inhibitor AP18 was used to distinguish between SM-induced and TRPA1-mediated or TRPA1-independent effects. Cells were exposed to 600 µM SM and proteome changes were investigated 24 h afterwards by 2D gel electrophoresis. Protein spots with differential staining levels were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and nano liquid chromatography electrospray ionization tandem mass spectrometry. Results were verified by RT-qPCR experiments in both HEKA1 or A549 cells. Heat shock 70 kDa protein 6 (HSPA6) was identified as an SM-induced and TRPA1-mediated protein. AP18 pre-treatment diminished the up-regulation. RT-qPCR measurements verified these results and further revealed a time-dependent regulation. Our results demonstrate that SM-mediated activation of TRPA1 influences the protein expression and confirm the important role of TRPA1 ion channels in the molecular toxicology of SM.
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Affiliation(s)
- Robin Lüling
- Bundeswehr Institute of Pharmacology and Toxicology, Ludwig-Maximilians-Universität Munich, 80937 Munich, Germany.
- Walther-Straub-Institute of Pharmacology and Toxicology, Ludwig-Maximilians-Universität Munich, 80336 Munich, Germany.
| | - Harald John
- Bundeswehr Institute of Pharmacology and Toxicology, Ludwig-Maximilians-Universität Munich, 80937 Munich, Germany.
| | - Thomas Gudermann
- Walther-Straub-Institute of Pharmacology and Toxicology, Ludwig-Maximilians-Universität Munich, 80336 Munich, Germany.
| | - Horst Thiermann
- Bundeswehr Institute of Pharmacology and Toxicology, Ludwig-Maximilians-Universität Munich, 80937 Munich, Germany.
| | - Harald Mückter
- Walther-Straub-Institute of Pharmacology and Toxicology, Ludwig-Maximilians-Universität Munich, 80336 Munich, Germany.
| | - Tanja Popp
- Bundeswehr Institute of Pharmacology and Toxicology, Ludwig-Maximilians-Universität Munich, 80937 Munich, Germany.
- Walther-Straub-Institute of Pharmacology and Toxicology, Ludwig-Maximilians-Universität Munich, 80336 Munich, Germany.
| | - Dirk Steinritz
- Bundeswehr Institute of Pharmacology and Toxicology, Ludwig-Maximilians-Universität Munich, 80937 Munich, Germany.
- Walther-Straub-Institute of Pharmacology and Toxicology, Ludwig-Maximilians-Universität Munich, 80336 Munich, Germany.
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A Proposed Molecular Mechanism for Physical Analgesia in Chronic Pain. Neural Plast 2018; 2018:1260285. [PMID: 29887879 PMCID: PMC5985137 DOI: 10.1155/2018/1260285] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2017] [Revised: 03/22/2018] [Accepted: 03/27/2018] [Indexed: 12/20/2022] Open
Abstract
Although pain is indispensable for survival, chronic pain places a heavy burden on humans. As the efficacy of opioid treatment is limited, the development of alternative methods of pain relief without medication is desirable. Recently, we have developed a novel method of physical analgesia using an adhesive “pyramidal thorn patch.” When we apply about 3 trials of these patches on the skin of a pain region, the pain region moves toward the spinal cord like a “cutaneous rabbit,” and finally, the pain vanishes. In the present review, we propose a molecular mechanism for this analgesic method or pain relief following application of the pyramidal thorn patch where firstly the mechanoreceptors and their related nerves under the skin are activated in response to touch. Transient receptor potential (TRP) channels serve as mechanosensitive channels within these mechanoreceptors. We further propose that activation of the nerves connected with the mechanoreceptors releases oxytocin, which has an antinociceptive function and activates TRP channels to hyperpolarize the pain signal nerves. We believe that our system will pave the way for alternative pain treatment.
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Johnston RK, Snell TW. Moderately lower temperatures greatly extend the lifespan of Brachionus manjavacas (Rotifera): Thermodynamics or gene regulation? Exp Gerontol 2016; 78:12-22. [PMID: 26939542 PMCID: PMC4841702 DOI: 10.1016/j.exger.2016.02.014] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Revised: 02/19/2016] [Accepted: 02/25/2016] [Indexed: 01/30/2023]
Abstract
Environmental temperature greatly affects lifespan in a wide variety of animals, but the exact mechanisms underlying this effect are still largely unknown. A moderate temperature decrease from 22°C to 16°C extends the lifespan of the monogonont rotifer Brachionus manjavacas by up to 163%. Thermodynamic effects on metabolism contribute to this increase in longevity, but are not the only cause. When rotifers are exposed to 16°C for four days and then transfered to 22°C, they survive until day 13 at nearly identical rates as rotifers maintained at 16°C continuously. This persistence of the higher survival for nine days after transfer to 22°C suggests that low temperature exposure alters the expression of genes that affect the rate of aging. The relative persistence of the gene regulation effect suggests that it may play an even larger role in slowing aging than the thermodynamic effects. The life extending effects of these short-term low temperature treatments are largest when the exposure happens early in the life cycle, demonstrating the importance of early development. There is no advantage to lowering the temperature below 16°C to 11° or 5°C. Rotifers exposed to 16°C also displayed increased resistance to heat, starvation, oxidative and osmotic stress. Reproductive rates at 16°C were lower than those at 22°C, but because they reproduce longer, there is no significant change in the lifetime fecundity of females. To investigate which genes contribute to these effects, the expression of specific temperature sensing genes was knocked down using RNAi. Of 12 genes tested, RNAi knockdown of four eliminated the survival enhancing effects of the four-day cold treatment: TRP7, forkhead box C, Y-box factor, and ribosomal protein S6. This demonstrates that active gene regulation is an important factor in temperature mediated life extension, and that these particular genes play an integral role in these pathways. As a thermoresponsive sensor, TRP7 may be responsible for triggering the signaling cascade contributing to temperature mediated life extension. The TRP genes may also provide especially promising candidates for targeted gene manipulations or pharmacological interventions capable of mimicking the effects of low temperature exposure. These results support recent theories of aging that claim rate of aging is determined by an actively regulated genetic mechanism rather than an accumulation of molecular damage.
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Affiliation(s)
- Rachel K Johnston
- School of Biology, Georgia Institute of Technology, Atlanta, GA 30332-0230, USA.
| | - Terry W Snell
- School of Biology, Georgia Institute of Technology, Atlanta, GA 30332-0230, USA
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Derinat Protects Skin against Ultraviolet-B (UVB)-Induced Cellular Damage. Molecules 2015; 20:20297-311. [PMID: 26569211 PMCID: PMC6331914 DOI: 10.3390/molecules201119693] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2015] [Revised: 10/29/2015] [Accepted: 11/05/2015] [Indexed: 01/12/2023] Open
Abstract
Ultraviolet-B (UVB) is one of the most cytotoxic and mutagenic stresses that contribute to skin damage and aging through increasing intracellular Ca2+ and reactive oxygen species (ROS). Derinat (sodium deoxyribonucleate) has been utilized as an immunomodulator for the treatment of ROS-associated diseases in clinics. However, the molecular mechanism by which Derinat protects skin cells from UVB-induced damage is poorly understood. Here, we show that Derinat significantly attenuated UVB-induced intracellular ROS production and decreased DNA damage in primary skin cells. Furthermore, Derinat reduced intracellular ROS, cyclooxygenase-2 (COX-2) expression and DNA damage in the skin of the BALB/c-nu mice exposed to UVB for seven days in vivo. Importantly, Derinat blocked the transient receptor potential canonical (TRPC) channels (TRPCs), as demonstrated by calcium imaging. Together, our results indicate that Derinat acts as a TRPCs blocker to reduce intracellular ROS production and DNA damage upon UVB irradiation. This mechanism provides a potential new application of Derinat for the protection against UVB-induced skin damage and aging.
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Ito E. Preface of Special Issue "TRP channels: their functional roles in medical sciences". Biophysics (Nagoya-shi) 2015; 11:7-8. [PMID: 27493508 PMCID: PMC4736794 DOI: 10.2142/biophysics.11.7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Affiliation(s)
- Etsuro Ito
- Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Sanuki 769-2193, Japan
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