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https://www.readbyqxmd.com/read/28185894/trpc1-and-trpc4-channels-functionally-interact-with-stim1l-to-promote-myogenesis-and-maintain-fast-repetitive-ca-2-release-in-human-myotubes
#1
Fabrice Antigny, Jessica Sabourin, Sophie Saüc, Laurent Bernheim, Stéphane Koenig, Maud Frieden
STIM1 and Orai1 are essential players of store-operated Ca(2+) entry (SOCE) in human skeletal muscle cells and are required for adult muscle differentiation. Besides these two proteins, TRPC (transient receptor potential canonical) channels and STIM1L (a longer STIM1 isoform) are also present on muscle cells. In the present study, we assessed the role of TRPC1, TRPC4 and STIM1L in SOCE, in the maintenance of repetitive Ca(2+) transients and in muscle differentiation. Knockdown of TRPC1 and TRPC4 reduced SOCE by about 50% and significantly delayed the onset of Ca(2+) entry, both effects similar to STIM1L invalidation...
February 6, 2017: Biochimica et Biophysica Acta
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
#2
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/28074011/new-connections-nherf-gates-activity
#3
Nancy R Gough
The NHERF molecular adaptors serve as gates for TRPC4 and TRPC5 regulation by diacylglycerol and recognition of CFTR by the quality control checkpoint.
January 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28066150/calcium-permeability-of-transient-receptor-potential-canonical-trpc-4-channels-measured-by-trpc4-gcamp6s
#4
Juyeon Ko, Jongyun Myeong, Dongki Yang, Insuk So
Conflicting evidence has been obtained regarding whether transient receptor potential cation channels (TRPC) are store-operated channels (SOCs) or receptor-operated channels (ROCs). Moreover, the Ca/Na permeability ratio differs depending on whether the current-voltage (I-V) curve has a doubly rectifying shape or inward rectifying shape. To investigate the calcium permeability of TRPC4 channels, we attached GCaMP6s to TRPC4 and simultaneously measured the current and calcium signals. A TRPC4 specific activator, (-)-englerin A, induced both current and calcium fluorescence with the similar time course...
January 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/27994151/dynamic-nherf-interaction-with-trpc4-5-proteins-is-required-for-channel-gating-by-diacylglycerol
#5
Ursula Storch, Anna-Lena Forst, Franziska Pardatscher, Serap Erdogmus, Maximilian Philipp, Manuel Gregoritza, Michael Mederos Y Schnitzler, Thomas Gudermann
The activation mechanism of the classical transient receptor potential channels TRPC4 and -5 via the Gq/11 protein-phospholipase C (PLC) signaling pathway has remained elusive so far. In contrast to all other TRPC channels, the PLC product diacylglycerol (DAG) is not sufficient for channel activation, whereas TRPC4/5 channel activity is potentiated by phosphatidylinositol 4,5-bisphosphate (PIP2) depletion. As a characteristic structural feature, TRPC4/5 channels contain a C-terminal PDZ-binding motif allowing for binding of the scaffolding proteins Na(+)/H(+) exchanger regulatory factor (NHERF) 1 and 2...
January 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27992507/trpc4%C3%AE-and-trpc4%C3%AE-similarly-affect-neonatal-cardiomyocyte-survival-during-chronic-gpcr-stimulation
#6
Nadine Kirschmer, Sandra Bandleon, Viktor von Ehrlich-Treuenstätt, Sonja Hartmann, Alice Schaaf, Anna-Karina Lamprecht, Erick Miranda-Laferte, Tanja Langsenlehner, Oliver Ritter, Petra Eder
The Transient Receptor Potential Channel Subunit 4 (TRPC4) has been considered as a crucial Ca2+ component in cardiomyocytes promoting structural and functional remodeling in the course of pathological cardiac hypertrophy. TRPC4 assembles as homo or hetero-tetramer in the plasma membrane, allowing a non-selective Na+ and Ca2+ influx. Gαq protein-coupled receptor (GPCR) stimulation is known to increase TRPC4 channel activity and a TRPC4-mediated Ca2+ influx which has been regarded as ideal Ca2+ source for calcineurin and subsequent nuclear factor of activated T-cells (NFAT) activation...
2016: PloS One
https://www.readbyqxmd.com/read/27875305/-englerin-a-evoked-cytotoxicity-is-mediated-by-na-influx-and-counteracted-by-na-k-atpase
#7
Melanie J Ludlow, Hannah J Gaunt, Hussein N Rubaiy, Katie E Musialowski, Nicola M Blythe, Naveen S Vasudev, Katsuhiko Muraki, David J Beech
(-)-Englerin A ((-)-EA) has a rapid and potent cytotoxic effect on several types of cancer cell that is mediated by plasma membrane ion channels containing transient receptor potential canonical 4 (TRPC4) protein. Because these channels are Ca(2+)-permeable, it was initially thought that the cytotoxicity arose as a consequence of Ca(2+) overload. Here we show that this is not the case and that the effect of (-)-EA is mediated by a heteromer of TRPC4 and TRPC1 proteins. Both TRPC4 and TRPC1 were required for (-)-EA cytotoxicity; however, although TRPC4 was necessary for the (-)-EA-evoked Ca(2+) elevation, TRPC1 was not...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27854075/benzimidazole-derivative-m084-extends-the-lifespan-of-caenorhabditis-elegans-in-a-daf-16-foxo-dependent-way
#8
Ai-Jun Ding, Gui-Sheng Wu, Bin Tang, Xuechuan Hong, Michael X Zhu, Huai-Rong Luo
With the growth of aging population, there is increasing demand to develop strategy to improve the aging process and aging-related diseases. Benzimidazole and its derivatives are crucial heterocyclic backbone of many drugs and compounds with diverse therapeutic applications, including alleviation of aging-related diseases. Here, we investigate if the benzimidazole derivative n-butyl-[1H]-benzimidazol-2-amine (M084), a novel inhibitor of TRPC4 and TRPC5 channels and antidepressant, could affect the lifespan of Caenorhabditis elegans (C...
February 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27617218/identification-of-trpcs-genetic-variants-that-modify-risk-for-lung-cancer-based-on-the-pathway-and-two-stage-study
#9
Zili Zhang, Jian Wang, Jianxing He, Xiansheng Zeng, Xindong Chen, Mingmei Xiong, Qipeng Zhou, Meihua Guo, Defu Li, Wenju Lu
OBJECTIVE: Store operated calcium channels (SOCCs) and Receptor-operated calcium channels (ROCCs) are important pathways participating in regulation of intracellular Ca(2 +) concentration in various cell types. The purpose of our study is to determine whether genetic variations in key components of SOCCs and ROCCs are associated with lung cancer risk. METHODS: We identified 236 tagSNPs in 9 key genes related to SOCCs and ROCCs (TRPC1, TRPC3, TRPC4, TRPC6, TRPC7, ORAI1, ORAI2, STIM1, and STIM2) and evaluated their association with lung cancer risk in a two-stage case-control study with a total of 2433 lung cancer cases and 2433 cancer-free controls using Illumina high throughput genotyping platform...
September 2016: Meta Gene
https://www.readbyqxmd.com/read/27614169/endoglin-selectively-modulates-transient-receptor-potential-channel-expression-in-left-and-right-heart-failure
#10
Kevin J Morine, Vikram Paruchuri, Xiaoying Qiao, Mark Aronovitz, Gordon S Huggins, David DeNofrio, Michael S Kiernan, Richard H Karas, Navin K Kapur
INTRODUCTION: Transient receptor potential (TRP) channels are broadly expressed cation channels that mediate diverse physiological stimuli and include canonical (TRPC), melastatin (TRPM), and vanilloid (TRPV) subtypes. Recent studies have implicated a role for TRPC6 channels as an important component of signaling via the cytokine, transforming growth factor beta 1 (TGFβ1) in right (RV) or left ventricular (LV) failure. Endoglin (Eng) is a transmembrane glycoprotein that promotes TRPC6 expression and TGFβ1 activity...
November 2016: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/27471122/upregulation-of-transient-receptor-potential-canonical-channels-contributes-to-endotoxin-induced-pulmonary-arterial-stenosis
#11
Gui-Lan Chen, Hongni Jiang, Fangdong Zou
BACKGROUND Septic shock is a pathologic condition caused by endotoxin-producing bacteria, and often associated with severe pulmonary hypertension. Inflammation is a major systemic response to endotoxin; however, it is unknown whether endotoxin has a direct impact on pulmonary arteries that contributes to pathogenesis of pulmonary hypertension. MATERIAL AND METHODS Rat pulmonary arteries and primary pulmonary arterial smooth muscle cells (PASMCs) were cultured in vitro and treated with lipopolysaccharide (LPS) and blockers of transient receptor potential canonical (TRPC) channels...
July 29, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27470334/lipopolysaccharide-potentiates-endothelin-1-induced-proliferation-of-pulmonary-arterial-smooth-muscle-cells-by-upregulating-trpc-channels
#12
Hong-Ni Jiang, Bo Zeng, Gui-Lan Chen, Bin Lai, Shao-Hua Lu, Jie-Ming Qu
Lipopolysaccharide (LPS) and endothelin-1 (ET-1) are critical pathogenic factors in sepsis-induced pulmonary hypertension; however it is unknown whether they have a coordinated action in the pathogenesis of this disease. Here we found that although LPS did not change the contractility of rat pulmonary arterial smooth muscle cells (PASMCs) in response to ET-1, it significantly promoted ET-1-induced PASMC proliferation. Measurement of ET-1-evoked Ca(2+) transients in PASMCs showed that LPS dramatically enhanced Ca(2+) influx mediated by transient receptor potential canonical (TRPC) channels...
August 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27422996/endothelial-hyperpermeability-in-severe-pulmonary-arterial-hypertension-role-of-store-operated-calcium-entry
#13
Chun Zhou, Mary I Townsley, Mikhail Alexeyev, Norbert F Voelkel, Troy Stevens
Here, we tested the hypothesis that animals with severe pulmonary arterial hypertension (PAH) display increased sensitivity to vascular permeability induced by activation of store-operated calcium entry. To test this hypothesis, wild-type and transient receptor potential channel 4 (TRPC4) knockout Fischer 344 rats were given a single injection of Semaxanib (SU5416; 20 mg/kg) followed by 3 wk of exposure to hypoxia (10% oxygen) and a return to normoxia (21% oxygen) for an additional 2-3 wk. This Semaxanib/hypoxia/normoxia (i...
September 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27289383/transient-receptor-potential-canonical-4-and-5-proteins-as-targets-in-cancer-therapeutics
#14
REVIEW
Hannah J Gaunt, Naveen S Vasudev, David J Beech
Novel approaches towards cancer therapy are urgently needed. One approach might be to target ion channels mediating Ca(2+) entry because of the critical roles played by Ca(2+) in many cell types, including cancer cells. There are several types of these ion channels, but here we address those formed by assembly of transient receptor potential canonical (TRPC) proteins, particularly those which involve two closely related members of the family: TRPC4 and TRPC5. We focus on these proteins because recent studies point to roles in important aspects of cancer: drug resistance, transmission of drug resistance through extracellular vesicles, tumour vascularisation, and evoked cancer cell death by the TRPC4/5 channel activator (-)-englerin A...
October 2016: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/27287524/muscarinic-receptor-induced-contractions-of-the-detrusor-are-mediated-by-activation-of-trpc4-channels
#15
Caoimhin S Griffin, Eamonn Bradley, Srikanth Dudem, Mark A Hollywood, Noel G McHale, Keith D Thornbury, Gerard P Sergeant
PURPOSE: Muscarinic receptor mediated contractions of the detrusor rely on Ca(2+) influx through voltage-gated Ca(2+) channels but to our knowledge the mechanism linking stimulation of M3Rs to the activation of voltage dependent Ca(2+) channels has not been established. TRPC4 channels are receptor operated cation channels that couple muscarinic receptor activation to depolarization of intestinal smooth muscle cells, voltage-activated Ca(2+) influx and contraction. We investigated whether TRPC4 channels are involved in cholinergic mediated contractions of the detrusor...
June 7, 2016: Journal of Urology
https://www.readbyqxmd.com/read/27165284/erratum-to-intracellular-spermine-blocks-trpc4-channel-via-electrostatic-interaction-with-c-terminal-negative-amino-acids
#16
Jinsung Kim, Sang Hui Moon, Young-Cheul Shin, Ju-Hong Jeon, Kyu Joo Park, Kyu Pil Lee, Insuk So
No abstract text is available yet for this article.
May 10, 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27131740/the-interaction-domains-of-transient-receptor-potential-canonical-trpc-1-4-and-trpc1-5-heteromultimeric-channels
#17
Jongyun Myeong, Juyeon Ko, Chansik Hong, Dongki Yang, Kyu Pil Lee, Ju-Hong Jeon, Insuk So
Transient receptor potential canonical (TRPC) family contains a non-selective cation channel, and four TRPC subunits form a functional tetrameric channel. TRPC4/5 channels form not only the homotetrameric channel but also a heterotetrameric channel with TRPC1. We investigated the interaction domain required for TRPC1/4 or TRPC1/5 heteromultimeric channels using FRET and the patch-clamp technique. TRPC1 only localized at the plasma membrane (PM) when it was coexpressed with TRPC4 or TRPC5. The TRPC1/4 or TRPC1/5 heteromultimeric showed the typical outward rectifying I/V curve...
June 3, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27129253/transient-receptor-potential-canonical-trpc-orai1-dependent-store-operated-ca2-channels-new-targets-of-aldosterone-in-cardiomyocytes
#18
Jessica Sabourin, Fiona Bartoli, Fabrice Antigny, Ana Maria Gomez, Jean-Pierre Benitah
Store-operated Ca(2+) entry (SOCE) has emerged as an important mechanism in cardiac pathology. However, the signals that up-regulate SOCE in the heart remain unexplored. Clinical trials have emphasized the beneficial role of mineralocorticoid receptor (MR) signaling blockade in heart failure and associated arrhythmias. Accumulated evidence suggests that the mineralocorticoid hormone aldosterone, through activation of its receptor, MR, might be a key regulator of Ca(2+) influx in cardiomyocytes. We thus assessed whether and how SOCE involving transient receptor potential canonical (TRPC) and Orai1 channels are regulated by aldosterone/MR in neonatal rat ventricular cardiomyocytes...
June 17, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27099524/natural-killer-cells-and-single-nucleotide-polymorphisms-of-specific-ion-channels-and-receptor-genes-in-myalgic-encephalomyelitis-chronic-fatigue-syndrome
#19
Sonya Marshall-Gradisnik, Teilah Huth, Anu Chacko, Samantha Johnston, Pete Smith, Donald Staines
AIM: The aim of this paper was to determine natural killer (NK) cytotoxic activity and if single nucleotide polymorphisms (SNPs) and genotypes in transient receptor potential (TRP) ion channels and acetylcholine receptors (AChRs) were present in isolated NK cells from previously identified myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) patients. SUBJECTS AND METHODS: A total of 39 ME/CFS patients (51.69±2 years old) and 30 unfatigued controls (47...
2016: Application of Clinical Genetics
https://www.readbyqxmd.com/read/27083517/transient-receptor-potential-channel-4-encodes-a-vascular-permeability-defect-and-high-frequency-ca-2-transients-in-severe-pulmonary-arterial-hypertension
#20
Michael Francis, Ningyong Xu, Chun Zhou, Troy Stevens
The canonical transient receptor potential channel 4 (TRPC4) comprises an endothelial store-operated Ca(2+) entry channel, and TRPC4 inactivation confers a survival benefit in pulmonary arterial hypertension (PAH). Endothelial Ca(2+) signals mediated by TRPC4 enhance vascular permeability in vitro, but the contribution of TRPC4-dependent Ca(2+) signals to the regulation of endothelial permeability in PAH is poorly understood. We tested the hypothesis that TRPC4 increases vascular permeability and alters the frequency of endothelial Ca(2+) transients in PAH...
June 2016: American Journal of Pathology
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