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https://www.readbyqxmd.com/read/28325835/picomolar-selective-and-subtype-specific-small-molecule-inhibition-of-trpc1-4-5-channels
#1
Hussein N Rubaiy, Melanie J Ludlow, Matthias Henrot, Hannah J Gaunt, Katarina Miteva, Sin Yin Cheung, Yasuyuki Tanahashi, Nurasyikin Hamzah, Katie E Musialowski, Nicola M Blythe, Hollie L Appleby, Marc A Bailey, Lynn McKeown, Roger Taylor, Richard Foster, Herbert Waldmann, Peter Nussbaumer, Mathias Christmann, Robin S Bon, Katsuhiko Muraki, David J Beech
The concentration of free cytosolic Ca(2+) and the voltage across the plasma membrane are major determinants of cell function. Ca(2+)-permeable non-selective cationic channels are known to regulate these parameters but understanding of these channels remains inadequate. Here we focus on Transient Receptor Potential Canonical 4 and 5 proteins (TRPC4 and TRPC5) which assemble as homomers or heteromerize with TRPC1 to form Ca(2+)-permeable non-selective cationic channels in many mammalian cell types. Multiple roles have been suggested including in epilepsy, innate fear, pain and cardiac remodeling but limitations in tools to probe these channels have restricted progress...
March 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28314576/trpc6-and-kidney-disease-sclerosing-more-than-just-glomeruli
#2
Johannes Schlondorff
Fibrosis is a common response to injury but can also perpetuate tissue dysfunction. Transient receptor potential C6 (TRPC6) is implicated in cardiac and skin healing via regulation of myofibroblast differentiation. Wu et al. now demonstrate a role for TRPC6 in renal fibrosis, via a mechanism that also relies on TRPC3 and is antagonized by soluble klotho. Modulation of TRPC3/6 activity may provide a means of dampening the fibrotic response involved in chronic kidney disease progression.
April 2017: Kidney International
https://www.readbyqxmd.com/read/28300348/sphingosine-1-phosphate-induces-ca-2-signaling-and-cxcl1-release-via-trpc6-channel-in-astrocytes
#3
Hisashi Shirakawa, Rumi Katsumoto, Shota Iida, Takahito Miyake, Takuya Higuchi, Takuya Nagashima, Kazuki Nagayasu, Takayuki Nakagawa, Shuji Kaneko
A biologically active lipid, sphingosine-1-phosphate (S1P) is highly abundant in blood, and plays an important role in regulating the growth, survival, and migration of many cells. Binding of the endogenous ligand S1P results in activation of various signaling pathways via G protein-coupled receptors, some of which generates Ca(2+) mobilization. In astrocytes, S1P is reported to evoke Ca(2+) signaling, proliferation, and migration; however, the precise mechanisms underlying such responses in astrocytes remain to be elucidated...
March 16, 2017: Glia
https://www.readbyqxmd.com/read/28292887/orai-and-trpc-channel-characterization-in-fc%C3%AE%C2%B5ri-mediated-calcium-signaling-and-mediator-secretion-in-human-mast-cells
#4
Hannah E Wajdner, Jasmine Farrington, Claire Barnard, Peter T Peachell, Christine G Schnackenberg, Joseph P Marino, Xiaoping Xu, Karen Affleck, Malcolm Begg, Elizabeth P Seward
Inappropriate activation of mast cells via the FcεRI receptor leads to the release of inflammatory mediators and symptoms of allergic disease. Calcium influx is a critical regulator of mast cell signaling and is required for exocytosis of preformed mediators and for synthesis of eicosanoids, cytokines and chemokines. Studies in rodent and human mast cells have identified Orai calcium channels as key contributors to FcεRI-initiated mediator release. However, until now the role of TRPC calcium channels in FcεRI-mediated human mast cell signaling has not been published...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28274093/canonical-transient-receptor-potential-channels-and-their-link-with-cardio-cerebro-vascular-diseases
#5
REVIEW
Xiong Xiao, Hui-Xia Liu, Kuo Shen, Wei Cao, Xiao-Qiang Li
The canonical transient receptor potential channels (TRPCs) constitute a series of nonselective cation channels with variable degrees of Ca²⁺ selectivity. TRPCs consist of seven mammalian members, TRPC1, TRPC2, TRPC3, TRPC4, TRPC5, TRPC6, and TRPC7, which are further divided into four subtypes, TRPC1, TRPC2, TRPC4/5, and TRPC3/6/7. These channels take charge of various essential cell functions such as contraction, relaxation, proliferation, and dysfunction. This review, organized into seven main sections, will provide an overview of current knowledge about the underlying pathogenesis of TRPCs in cardio/cerebrovascular diseases, including hypertension, pulmonary arterial hypertension, cardiac hypertrophy, atherosclerosis, arrhythmia, and cerebrovascular ischemia reperfusion injury...
March 10, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28263796/insulin-increases-filtration-barrier-permeability-via-trpc6-dependent-activation-of-pkgi%C3%AE-signaling-pathways
#6
Dorota Rogacka, Irena Audzeyenka, Patrycja Rachubik, Michał Rychłowski, Małgorzata Kasztan, Maciej Jankowski, Stefan Angielski, Agnieszka Piwkowska
Podocytes are dynamic polarized cells on the surface of glomerular capillaries and an essential component of the glomerular filtration barrier. Insulin increases the activation of protein kinase G type Iα (PKGIα) subunits, leading to podocyte dysfunction. In addition, accumulating evidence suggests that TRPC6 channels are crucial mediators of podocyte calcium handling and involved in the regulation of glomerular filtration. Therefore, we investigated whether TRPC6 is involved in the regulation of filtration barrier permeability by insulin via the PKGIα-dependent manner...
March 2, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28242818/characterization-of-flow-regulated-cortical-collecting-duct-endothelin-1-production
#7
Nirupama Ramkumar, Yang Gao, Donald E Kohan
Collecting duct (CD) endothelin-1 (ET-1) is an autocrine inhibitor of Na(+) and water reabsorption. Salt or water loading increases CD ET-1 production; this is likely due, at least in part, to increased tubule fluid flow. The mechanisms by which flow stimulates CD ET-1 production are incompletely understood. In particular, flow induction of cortical CD (CCD) and inner medullary CD (IMCD) ET-1 synthesis may occur via different mechanisms. Since flow-mediated ET-1 production in IMCD has been more extensively characterized than in the CCD, this study was undertaken to further examine putative signaling pathways involved in flow-stimulated CCD ET-1 production...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28218578/bone-marrow-derived-mesenchymal-stem-cells-ameliorate-nephrosis-through-repair-of-impaired-podocytes
#8
Yi Chen, Jun Chen, Jianxin Wan, Na Gao, Jiong Cui, Danyu You, Zhenhuan Zou
PURPOSE: The purpose of this study was to investigate the effects of bone marrow-derived mesenchymal stem cells (BMSC) on podocytes of puromycin amino nuclear glucoside (PAN) -induced nephrosis in mice. METHODS: Mice were randomly divided into Control, PAN and BMSC groups. Mice were injected with PAN (0.5 mg/g weight) via the tail vein. The 24-h urinary protein was obtained after modelling, and urinary protein excretion was determined. The blood and kidney specimens were isolated after the tenth day of modelling...
February 19, 2017: Clinical and Investigative Medicine. Médecine Clinique et Experimentale
https://www.readbyqxmd.com/read/28217875/mechanisms-of-pruritogen-induced-activation-of-itch-nerves-in-isolated-mouse-skin
#9
F Ru, H Sun, D Jurcakova, R A Herbstsomer, J Meixong, X Dong, B J Undem
Chloroquine (CQ) and histamine are pruritogens commonly used to study itch in the mouse. A novel skin-nerve preparation was used to evaluate chloroquine (CQ)- and histamine- induced activation of afferent nerves in the dorsal thoracic skin of the mouse. All CQ sensitive nerves were C-fibres, and were also sensitive to histamine. The response to CQ, but not histamine, was largely absent in mrgpr cluster Δ -/- mice supporting the hypothesis that CQ evokes itch largely via stimulation of MrgprA3 receptors. The CQ-induced action potential discharge was largely absent in phospholipase Cβ3 knockout animals...
February 19, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28217807/-role-of-trpc6-in-pulmonary-artery-smooth-muscle-cells-proliferation-and-apoptosis-under-hypoxia-and-hypercapnia
#10
Xu-Guang Jia, Meng-Xiao Zheng, Jing-Jing Zhang, Cong-Cong Zhang, Mei-Ping Zhao, Yi-Ming Wu, Xi-Wen Chen, Wan-Tie Wang
The present study was to investigate the role of TRPC6 in pulmonary artery smooth muscle cells (PASMCs) proliferation and apoptosis under hypoxia and hypercapnia. PASMCs were isolated from chloral hydrate-anesthetized male Sprague-Dawley (SD) rats. Cellular purity was assessed by immunofluorescence staining for smooth muscle α-actin under fluorescence microscopy. Passage 4-6 PASMCs were starved for 24 h in serum-free DMEM and divided into 5 groups randomly: normoxia, hypoxia and hypercapnia, DMSO, TRPC6 inhibitor SKF-96365 and TRPC6 activator OAG groups...
February 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28214865/inhibition-of-trpc6-signal-pathway-alleviates-podocyte-injury-induced-by-tgf-%C3%AE-1
#11
Haiting Huang, Yanwu You, Xu Lin, Chunrong Tang, Xiangjun Gu, Meiying Huang, Youling Qin, Junhua Tan, Feifan Huang
BACKGROUND/AIMS: Transforming growth factor beta 1 (TGF-β1) plays a critical role in the pathogenesis of glomerulosclerosis. The purpose of this study was to examine the effects of inhibition of transient receptor potential cation channel C6 (TRPC6) on podocyte injury induced by TGF-β1 via nephrin and desmin mechanisms. METHODS: A rat model of nephropathy was first induced by intravenous injections of adriamycin to determine TRPC6 signal pathway engaged in glomerulosclerosis in vivo...
January 18, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28210627/hyperforin-hp-%C3%AE-cyclodextrin-enhances-mechanosensitive-ca-2-signaling-in-hacat-keratinocytes-and-in-atopic-skin-ex-vivo-which-accelerates-wound-healing
#12
Hiroya Takada, Jun Yonekawa, Masami Matsumoto, Kishio Furuya, Masahiro Sokabe
Cutaneous wound healing is accelerated by mechanical stretching, and treatment with hyperforin, a major component of a traditional herbal medicine and a known TRPC6 activator, further enhances the acceleration. We recently revealed that this was due to the enhancement of ATP-Ca(2+) signaling in keratinocytes by hyperforin treatment. However, the low aqueous solubility and easy photodegradation impede the topical application of hyperforin for therapeutic purposes. We designed a compound hydroxypropyl-β-cyclodextrin- (HP-β-CD-) tetracapped hyperforin, which had increased aqueous solubility and improved photoprotection...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28204945/spectrum-of-mutations-in-chinese-children-with-steroid-resistant-nephrotic-syndrome
#13
Fang Wang, Yanqin Zhang, Jianhua Mao, Zihua Yu, Zhuwen Yi, Li Yu, Jun Sun, Xiuxiu Wei, Fangrui Ding, Hongwen Zhang, Huijie Xiao, Yong Yao, Weizhen Tan, Svjetlana Lovric, Jie Ding, Friedhelm Hildebrandt
BACKGROUND: The aim of this study was to elucidate whether genetic screening test results of pediatric patients with steroid-resistant nephrotic syndrome (SRNS) vary with ethnicity. METHODS: Using high-throughput DNA sequencing, 28 nephrotic syndrome-related genes were analyzed in 110 chil-dren affected by SRNS and 10 children with isolated proteinuria enrolled by 5 centers in China (67 boys, 53 girls). Their age at disease onset ranged from 1 day to 208 months (median, 48...
February 15, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28124739/the-regulation-of-transient-receptor-potential-canonical-4-trpc4-channel-by-phosphodiesterase-5-inhibitor-via-the-cyclic-guanosine-3-5-monophosphate
#14
Jinhong Wie, SeungJoo Jeong, Misun Kwak, Jongyun Myeong, MeeRee Chae, Jong Kwan Park, Sung Won Lee, Insuk So
The transient receptor potential (TRP) protein superfamily consists of a diverse group of cation channels that bear structural similarities to the fruit fly Drosophila TRP. The TRP superfamily is distinct from other groups of ion channels in displaying a large diversity in ion selectivity, modes of activation, and physiological functions. Classical TRP (transient receptor potential canonical (TRPC)) channels are activated by stimulation of Gq-PLC-coupled receptors and modulated by phosphorylation. The cyclic guanosine monophosphate (cGMP)-PKG pathway is involved in the regulation of TRPC3 and TRPC6 channels...
January 26, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28110963/hyperforin-activates-gene-transcription-involving-transient-receptor-potential-c6-channels
#15
Gerald Thiel, Oliver G Rössler
Hypericum perforatum is one of the most prominent medical plants. Hyperforin, a main ingredient of H. perforatum, has been shown to activate transient receptor potential canonical C6 (TRPC6) channels. Alternatively, it has been proposed that hyperforin functions as a protonophore in a TRPC6-independent manner. Here, we show that hyperforin stimulation activates the transcription factor AP-1 in HEK293 cells expressing TRPC6 (T6.11 cells), but did not substantially change the AP-1 activity in HEK293 cells lacking TRPC6...
January 19, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28107550/enhanced-trpc-channel-mediated-ca-2-influx-in-the-cells-with-phospholipase-c-%C3%AE-1-overexpression-its-possible-role-in-coronary-artery-spasm
#16
Kazuo Murakami, Tomohiro Osanai, Makoto Tanaka, Kimitaka Nishizaki, Takahiko Kinjo, Tomohiro Tanno, Yuji Ishida, Akiko Suzuki, Tomohide Endo, Hirofumi Tomita, Ken Okumura
We reported that coronary spasm was induced in the transgenic mice with the increased phospholipase C (PLC)-δ1 activity. We investigated the effect of enhanced PLC-δ1 on Ca(2+) influx and its underlying mechanisms. We used human embryonic kidney (HEK)-293 and coronary arteries-smooth-muscle cells (CASMC). Intracellular free Ca(2+) concentration ([Ca(2+) ]i ) (nM) was measured by fura-2, and Ca(2+) influx was evaluated by the increase in [Ca(2+) ]i after addition of extracellular Ca(2+) . Acetylcholine (ACh) was used to induce Ca(2+) influx...
January 20, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28077439/the-functional-expression-of-transient-receptor-potential-channels-in-the-mouse-endometrium
#17
Katrien De Clercq, Charlotte Van den Eynde, Aurélie Hennes, Rieta Van Bree, Thomas Voets, Joris Vriens
STUDY QUESTION: Does mouse endometrial epithelial cells and stromal cells have a similar transient receptor potential (TRP)-channel expression profile and to that found in the human endometrium? SUMMARY ANSWER: Mouse endometrial epithelial and stromal cells have a distinct TRP channel expression profile analogous to what has been found in human endometrium, and hence suggests the mouse a good model to investigate the role of TRP channels in reproduction. WHAT IS KNOWN ALREADY: An optimal intercellular communication between epithelial and stromal endometrial cells is crucial for successful reproduction...
January 6, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28062998/high-glucose-enhances-isoflurane-induced-neurotoxicity-by-regulating-trpc-dependent-calcium-influx
#18
ZhongJie Liu, ChangQing Ma, Wei Zhao, QingGuo Zhang, Rui Xu, HongFei Zhang, HongYi Lei, ShiYuan Xu
Isoflurane is a commonly used inhalational anesthetic that can induce neurotoxicity via elevating cytosolic calcium (Ca(2+)). High glucose regulates the expression of a family of non-selective cation channels termed transient receptor potential canonical (TRPC) channels that may contribute to Ca(2+) influx. In the present study, we investigated whether high glucose enhances isoflurane-induced neurotoxicity by regulating TRPC-dependent Ca(2+) influx. First, we evaluated toxic damage in mice primary cultured hippocampal neurons and human neuroblastoma cells (SH-SY5Y cells) after hyperglycemia and isoflurane exposure...
January 6, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28039055/tgf%C3%AE-1-induces-stress-fiber-formation-through-upregulation-of-trpc6-in-vascular-smooth-muscle-cells
#19
Soonbum Park, Sanghoon Lee, Eun-Jung Park, MinJi Kang, Insuk So, Ju-Hong Jeon, Jung Nyeo Chun
Aberrant transforming growth factor β1 (TGFβ1) signaling plays a crucial role in the pathogenesis of vascular fibrosis. On the other hand, deregulated transient receptor potential canonical 6 (TRPC6) channel expression shows impaired vascular physiology and wound healing. However, it has little been known about the functional association between TGFβ1 and TRPC6 in vascular smooth muscle cells (VSMCs). In this study, we analyzed the microarray data obtained from TGFβ1-treated A7r5 VSMCs. We found that TGFβ1 specifically elevates the expression level of TRPC6 mainly through Smad-dependent canonical pathway...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28034782/spinal-trpc6-channels-contributes-to-morphine-induced-antinociceptive-tolerance-and-hyperalgesia-in-rats
#20
Hua Jin, Ying-Tong Sun, Guang-Qiong Guo, Da-Lin Chen, Yu-Jin Li, Gao-Peng Xiao, Xin-Nan Li
The chronic administration of opioids results in the development of morphine analgesic tolerance and withdrawl-induced hyperalgesia, which limits their clinical utility in pain treatment. However, the cellular mechanisms underlying opioid-induced tolerance and hyperalgesia are not fully understood. The transient receptor potential canonical channel TRPC6 is important for brain development and function, as it regulates cytosolic, endoplasmic reticulum, and mitochondrial Ca(2+) levels in neural cells. Here, we report that TRPC6 expression in the spinal cord was up-regulated after chronic morphine treatment...
February 3, 2017: Neuroscience Letters
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