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Alberto González, Claudio A Sáez, Bernardo Morales, Alejandra Moenne
The existence of functional Transient Receptor Potential (TRP) channels was analyzed in Ectocarpus siliculosus using agonists of human TRPs and specific antagonists of TRPA1, TRPC5, TRPM8 and TRPV; intracellular calcium was detected for 60 min. Increases in intracellular calcium were observed at 13, 29, 39 and 50-52 min, which appeared to be mediated by the activation of TRPM8/V1 at 13 min, TRPV1 at 29 min, TRPA1/V1 at 39 min and TRPA1/C5 at 50-52 min. In addition, intracellular calcium increases appear to be due to extracellular calcium entry, not requiring protein kinase activation...
March 2, 2018: Plant Physiology and Biochemistry: PPB
Teng Wang, Kuan Ning, Xu Sun, Chun Zhang, Lin-Fang Jin, Dong Hua
BACKGROUND: Elevated intracellular Ca2+ ([Ca2+ ]i ) level could lead to [Ca2+ ]i overload and promote apoptosis via different pathways. In our previously study, up-regulated expression of transient receptor potential canonical channel (TRPC5) was proven to increase [Ca2+ ]i level, and resulted in chemoresistance whereas not apoptosis in human colorectal cancer (CRC) cells. The ATP-dependent homeostatic maintenance of resting [Ca2+ ]i should be important in this process. Increased glycolysis was found to be an important adenosine triphosphate (ATP) source in cancer...
February 20, 2018: BMC Cancer
Stefan Just, Bertrand L Chenard, Angelo Ceci, Timothy Strassmaier, Jayhong A Chong, Nathaniel T Blair, Randall J Gallaschun, Donato Del Camino, Susan Cantin, Marc D'Amours, Christian Eickmeier, Christopher M Fanger, Carsten Hecker, David P Hessler, Bastian Hengerer, Katja S Kroker, Sam Malekiani, Robert Mihalek, Joseph McLaughlin, Georg Rast, JoAnn Witek, Achim Sauer, Christopher R Pryce, Magdalene M Moran
BACKGROUND: Forty million adults in the US suffer from anxiety disorders, making these the most common forms of mental illness. Transient receptor potential channel canonical subfamily (TRPC) members 4 and 5 are non-selective cation channels highly expressed in regions of the cortex and amygdala, areas thought to be important in regulating anxiety. Previous work with null mice suggests that inhibition of TRPC4 and TRPC5 may have anxiolytic effects. HC-070 IN VITRO: To assess the potential of TRPC4/5 inhibitors as an avenue for treatment, we invented a highly potent, small molecule antagonist of TRPC4 and TRPC5 which we call HC-070...
2018: PloS One
Jenny van der Wijst, René J M Bindels
No abstract text is available yet for this article.
January 22, 2018: Nature Reviews. Nephrology
Francesco Moccia
Intracellular Ca2+ signaling drives angiogenesis and vasculogenesis by stimulating proliferation, migration, and tube formation in both vascular endothelial cells and endothelial colony forming cells (ECFCs), which represent the only endothelial precursor truly belonging to the endothelial phenotype. In addition, local Ca2+ signals at the endoplasmic reticulum (ER)-mitochondria interface regulate endothelial cell fate by stimulating survival or apoptosis depending on the extent of the mitochondrial Ca2+ increase...
January 11, 2018: International Journal of Molecular Sciences
Hussein N Rubaiy, Tobias Seitz, Sven Hahn, Axel Choidas, Peter Habenberger, Bert Klebl, Klaus Dinkel, Peter Nussbaumer, Herbert Waldmann, Mathias Christmann, David J Beech
BACKGROUND AND PURPOSE: (-)-Englerin A (EA) is a potent cytotoxic agent against renal cell carcinoma cells. It achieves its effects by activation of TRPC4/TRPC1 heteromeric channels. It is also an agonist at channels formed by the related protein, TRPC5. Here we sought an EA analogue which might enable better understanding of these EA effects. EXPERIMENTAL APPROACH: Renal cell carcinoma A498 cells and HEK 293 cells overexpressing TRPC4 or TRPC5 were studied by intracellular Ca2+ measurement or whole-cell patch-clamp...
December 16, 2017: British Journal of Pharmacology
Yiming Zhou, Philip Castonguay, Eriene-Heidi Sidhom, Abbe R Clark, Moran Dvela-Levitt, Sookyung Kim, Jonas Sieber, Nicolas Wieder, Ji Yong Jung, Svetlana Andreeva, Jana Reichardt, Frank Dubois, Sigrid C Hoffmann, John M Basgen, Mónica S Montesinos, Astrid Weins, Ashley C Johnson, Eric S Lander, Michael R Garrett, Corey R Hopkins, Anna Greka
Progressive kidney diseases are often associated with scarring of the kidney's filtration unit, a condition called focal segmental glomerulosclerosis (FSGS). This scarring is due to loss of podocytes, cells critical for glomerular filtration, and leads to proteinuria and kidney failure. Inherited forms of FSGS are caused by Rac1-activating mutations, and Rac1 induces TRPC5 ion channel activity and cytoskeletal remodeling in podocytes. Whether TRPC5 activity mediates FSGS onset and progression is unknown. We identified a small molecule, AC1903, that specifically blocks TRPC5 channel activity in glomeruli of proteinuric rats...
December 8, 2017: Science
Jian Qiu, Martha A Bosch, Cecilia Meza, Uyen-Vy Navarro, Casey C Nestor, Edward J Wagner, Oline K Rønnekleiv, Martin J Kelly
Insulin resistance is at the core of the metabolic syndrome, and men exhibit a higher incidence of metabolic syndrome than women in early adult life, but this sex advantage diminishes sharply when women reach the postmenopausal state. Since 17β-estradiol (E2) augments the excitability of the anorexigenic POMC neurons, we investigated the neuroprotective effects of E2 against insulin resistance in POMC neurons from diet-induced obese (DIO) female and male mice. The efficacy of insulin to activate canonical transient receptor potential 5 (TRPC5) channels and depolarize POMC neurons was significantly reduced in DIO male but not in DIO female mice...
November 20, 2017: Endocrinology
M Wang, S Ji, G Shao, J Zhang, K Zhao, Z Wang, A Wu
PURPOSE: Exosomes are gradually detected as an indicator for diagnosis and prognosis of breast cancer in clinic and a systematic review was conducted. METHODS: A search for clinical studies published before July 1, 2017 was performed. Methods of exosome purification and identification from all studies were extracted. For diagnosis evaluation, the comparison of exosome biomarkers expression between breast cancer patients and healthy women was obtained; for prognosis prediction, the correlation between exosome biomarkers expression and chemotherapy resistance, overall survival (OS), disease-free survival (DFS), recurrence and metastasis of breast cancer was also extracted...
November 15, 2017: Clinical & Translational Oncology
Xuexiang Wang, Ranadheer R Dande, Hao Yu, Beata Samelko, Rachel E Miller, Mehmet M Altintas, Jochen Reiser
Transient receptor potential channel 5 (TRPC5) is highly expressed in brain and kidney and mediates calcium influx and promotes cell migration. In the kidney, loss of TRPC5 function has been reported to benefit kidney filter dynamics by balancing podocyte cytoskeletal remodeling. However, in vivo gain-in-function studies of TRPC5 with respect to kidney function have not been reported. To address this gap, we developed two transgenic mouse models on the C57BL/6 background by overexpressing either wild-type TRPC5 or a TRPC5 ion-pore mutant...
October 23, 2017: Journal of the American Society of Nephrology: JASN
John Wesley Maddox, Nikka Khorsandi, Evanna L Gleason
GABAergic signaling from amacrine cells (ACs) is a fundamental aspect of visual signal processing in the inner retina. We have previously shown that nitric oxide (NO) can elicit release of GABA independently from activation of voltage-gated Ca(2+) channels in cultured retinal ACs. This voltage-independent quantal GABA release relies on a Ca(2+) influx mechanism with pharmacological characteristics consistent with the involvement of transient receptor potential canonical (TRPC) channels TRPC4 and/or TRPC5. To determine the identity of these channels, we evaluate the ability of NO to elevate dendritic Ca(2+) and to stimulate GABA release from cultured ACs under conditions known to alter the function of TRPC4 and 5...
October 4, 2017: Journal of Neurophysiology
Petra Eder
TRPC channels have been suggested as potential candidates mediating store-operated Ca2+ entry (SOCE) in cardiomyocytes. There is increasing evidence that the TRPC isoforms TRPC1 and TRPC4 might fulfill the function as SOCs, in concert with or in parallel to the key players of SOCE, Orai1, and STIM1. Several other isoforms, e.g., TRPC3, TRPC6, and TRPC7, might rather associate to receptor-activated diacylglycerol (DAG)-sensitive ion channels. However, the exact activation mode has not been elucidated yet, given the characteristic of TRPC channels to heteromerize to unpredictable ion channel assemblies...
2017: Advances in Experimental Medicine and Biology
Zhen Chen, Yaodan Zhu, Yongfei Dong, Peng Zhang, Xiping Han, Jian Jin, Xin Ma
In cancer cells, intracellular Ca(2+) homeostasis is altered, and this is involved in tumor initiation, progression, and metastasis. However, little is known about the underlying mechanisms. Here, we report that transient receptor potential channel 5 (TrpC5), a receptor-activated non-selective Ca(2+) channel, is correlated with tumor metastasis in colon cancer patients. Moreover, in colon cancer cells, overexpression of TrpC5 caused a robust rise in the concentration of ([Ca(2+)]i), decreased E-cadherin, and increased mesenchymal biomarker expression, then promoted cell migration, invasion, and proliferation...
October 1, 2017: Clinical Science (1979-)
Irfan V Düzen, Fethi Yavuz, Ertan Vuruskan, Erhan Saracoglu, Fatih Poyraz, Hüseyin Göksülük, Basar Candemir, Seniz Demiryürek
Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is a major cause of morbidity and mortality. The upregulation of TRP channels is believed to mediate the progression of electrical remodelling and the arrhythmogenesis of the diseased heart. However, there is limited data about the contribution of the TRP channels to development of AF. The aim of this study was to investigate leukocyte TRP channels gene expressions in non-valvular atrial fibrillation (NVAF) patients. The study included 47 NVAF patients and 47 sex and age matched controls...
August 24, 2017: Scientific Reports
Pinaki Chaudhuri, Michael A Rosenbaum, Lutz Birnbaumer, Linda M Graham
Lipid oxidation products, including lysophosphatidylcholine (lysoPC), activate canonical transient receptor potential 6 (TRPC6) channels, and the subsequent increase in intracellular Ca2+ leads to TRPC5 activation. The goal of this study is to elucidate the steps in the pathway between TRPC6 activation and TRPC5 externalization. Following TRPC6 activation by lysoPC, extracellular regulated kinase (ERK) is phosphorylated. This leads to phosphorylation of p47phox and subsequent NADPH oxidase activation with increased production of reactive oxygen species...
November 1, 2017: American Journal of Physiology. Cell Physiology
Holger Beckmann, Julia Richter, Kerstin Hill, Nicole Urban, Horst Lemoine, Michael Schaefer
The transient receptor potential canonical channel 5 (TRPC5) is a Ca(2+)-permeable ion channel, which is predominantly expressed in the brain. TRPC5-deficient mice exhibit a reduced innate fear response and impaired motor control. In addition, outgrowth of hippocampal and cerebellar neurons is retarded by TRPC5. However, pharmacological evidence of TRPC5 function on cellular or organismic levels is sparse. Thus, there is still a need for identifying novel and efficient TRPC5 channel modulators. We, therefore, screened compound libraries and identified the glucocorticoid methylprednisolone and N-[3-(adamantan-2-yloxy)propyl]-3-(6-methyl-1,1-dioxo-2H-1λ(6),2,4-benzothiadiazin-3-yl)propanamide (BTD) as novel TRPC5 activators...
September 2017: Cell Calcium
Jenny Bröker-Lai, Astrid Kollewe, Barbara Schindeldecker, Jörg Pohle, Vivan Nguyen Chi, Ilka Mathar, Raul Guzman, Yvonne Schwarz, Alan Lai, Petra Weißgerber, Herbert Schwegler, Alexander Dietrich, Martin Both, Rolf Sprengel, Andreas Draguhn, Georg Köhr, Bernd Fakler, Veit Flockerzi, Dieter Bruns, Marc Freichel
Canonical transient receptor potential (TRPC) channels influence various neuronal functions. Using quantitative high-resolution mass spectrometry, we demonstrate that TRPC1, TRPC4, and TRPC5 assemble into heteromultimers with each other, but not with other TRP family members in the mouse brain and hippocampus. In hippocampal neurons from Trpc1/Trpc4/Trpc5-triple-knockout (Trpc1/4/5(-/-)) mice, lacking any TRPC1-, TRPC4-, or TRPC5-containing channels, action potential-triggered excitatory postsynaptic currents (EPSCs) were significantly reduced, whereas frequency, amplitude, and kinetics of quantal miniature EPSC signaling remained unchanged...
September 15, 2017: EMBO Journal
Jian Qiu, Edward J Wagner, Oline K Rønnekleiv, Martin J Kelly
Proopiomelanocortin (POMC) neurons within the hypothalamic arcuate nucleus are vital anorexigenic neurons. Both the insulin receptor and leptin receptor are coupled to activation of phosphatidylinositide-3 kinase (PI3K) to regulate multiple functions that increase POMC neuronal excitability. Using whole-cell recording in several mammalian species, we have found that both insulin and leptin depolarized POMC neurons via activation of TRPC5 channels. TRPC5 channels have been rigorously characterized as the downstream effector based on their biophysical properties, pharmacological profile and localization by immunocytochemistry and scRT-PCR...
July 4, 2017: Journal of Neuroendocrinology
Peng Zhang, Xiaoyu Liu, Hongjuan Li, Zhen Chen, Xiaoqiang Yao, Jian Jin, Xin Ma
Adriamycin is a first-line chemotherapy agent against cancer, but the development of resistance has become a major problem. Although autophagy is considered to be an adaptive survival response in response to chemotherapy and may be associated with chemoresistance, its inducer and the underlying molecular mechanisms remain unclear. Here, we demonstrate that adriamycin up-regulates the both levels of TRPC5 and autophagy, and the increase in autophagy is mediated by TRPC5 in breast cancer cells. Blockade of TRPC5 or autophagy increased the sensitivity to chemotherapy in vitro and in vivo...
June 9, 2017: Scientific Reports
Khadija M Alawi, David Tandio, Jin Xu, Pratish Thakore, Georgia Papacleovoulou, Elizabeth S Fernandes, Cristina Legido-Quigley, Catherine Williamson, Susan D Brain
Transient receptor potential canonical 5 (TRPC5), a calcium-permeable, non-selective cation channel is expressed in the periphery, but there is limited knowledge of its regulatory roles in vivo. Endogenous modulators of TRPC5 include a range of phospholipids that have an established role in liver disease, including lysophosphatidylcholine (LPC). Cholestasis is characterized by impairment of excretion of bile acids, leading to elevation of hepatic bile acids. We investigated the contribution of TRPC5 in a murine model of cholestasis...
May 24, 2017: Scientific Reports
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