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TRPC6

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https://www.readbyqxmd.com/read/29141922/trpc6-contributes-to-lps-induced-inflammation-through-erk1-2-and-p38-pathway-in-bronchial-epithelial-cells
#1
Li-Fen Zhou, Qing-Zi Chen, Chun-Tao Yang, Zhao-Di Fu, Shen-Ting Zhao, Yan Chen, Shu-Ni Li, Li Liao, Yu-Bo Zhou, Jian-Rong Huang, Jian-Hua Li
Transient receptor potential canonical (TRPC) channels are currently an emerging target for airway disorders. Recent evidences have indicated that TRPC6 as a member of the TRPC family plays an important role in airway inflammation, but its precise function in bronchial epithelial cells remains unclear. The aim of this study was to investigate the role of TRPC6 in TLR4-mediated inflammation in human bronchial epithelial cells stimulated by endotoxin (lipopolysaccharide, LPS). Hyp9 is a simplified phloroglucinol derivative of Hyperforin which highly selective activates TRPC6 channels...
November 15, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29104282/tetramethylpyrazine-protects-neurons-from-oxygen-glucose-deprivation-induced-death
#2
Zhengkai Shao, Lijun Wang, Shuang Liu, Xuefeng Wang
BACKGROUND To explore the theoretical basis for protecting the brain from ischemic stroke with tetramethylpyrazine, we studied whether and how tetramethylpyrazine could protect neurons against the oxygen-glucose deprivation (OGD)-induced death and whether transient receptor potential cation channel, subfamily C, member 6 (TRPC6) was involved. MATERIAL AND METHODS Primary rat cortical neurons were cultured and an OGD model was established in the presence or absence of tetramethylpyrazine. Neuronal death was assessed by measuring the uptake of membrane-impermeable PI...
November 6, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29050010/calcium-sensing-receptor-stimulation-in-cultured-glomerular-podocytes-induces-trpc6-dependent-calcium-entry-and-rhoa-activation
#3
Lei Zhang, Tianrong Ji, Qin Wang, Kexin Meng, Rui Zhang, He Yang, Chang Liao, Linlin Ma, Jundong Jiao
BACKGROUND/AIMS: Recent studies provided compelling evidence that stimulation of the calcium sensing receptor (CaSR) exerts direct renoprotective action at the glomerular podocyte level. This protective action may be attributed to the RhoA-dependent stabilization of the actin cytoskeleton. However, the underlying mechanisms remain unclear. METHODS: In the present study, an immortalized human podocyte cell line was used. Fluo-3 fluorescence was utilized to determine intracellular Ca2+ concentration ([Ca2+]i), and western blotting was used to measure canonical transient receptor potential 6 (TRPC6) protein expression and RhoA activity...
October 19, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29038887/mutations-in-inf2-may-be-associated-with-renal-histology-other-than-focal-segmental-glomerulosclerosis
#4
Anja K Büscher, Nora Celebi, Peter F Hoyer, Hanns-Georg Klein, Stefanie Weber, Julia Hoefele
BACKGROUND: In 2010, INF2 mutations were associated with autosomal-dominant focal segmental glomerulosclerosis (FSGS), clinically presenting with moderate proteinuria in adolescence. However, in the meantime, cases with more severe clinical courses have been described, including progression to end-stage renal disease (ESRD) during childhood. INF2 mutations in patients with isolated FSGS are clustered in exons 2 to 4, encoding the diaphanous inhibitory domain, involved in the regulation of the podocyte actin cytoskeleton...
October 6, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29021382/sustained-activation-of-guanylate-cyclase-a-with-tdt-a-natriuretic-peptide-derivative-exhibits-cardiorenal-protection-in-dahl-salt-sensitive-hypertensive-rats
#5
Shohei Oishi, Naoko Suzuki, Yuri Hasui, Tsuyoshi Homma, Masanori Obana, Takahiro Nagayama, Yasushi Fujio
Heart failure often presents with prognosis-relevant impaired renal function. To investigate whether the chronic activation of guanylate cyclase-A (GC-A) protects both heart and kidney, we examined the effects of TDT, a neprilysin (NEP)-resistant natriuretic peptide (NP) derivative, on cardiac and renal dysfunction in Dahl salt-sensitive hypertensive rats (DS rats). Pretreatment with NEP or NEP inhibitor did not influence GC-A activation by TDT both in vitro and in vivo, resulting in a long-acting profile of TDT compared to native human atrial NP (hANP)...
October 11, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28993502/cardiovascular-effects-of-renal-distal-tubule-deletion-of-the-fgf-receptor-1-gene
#6
Xiaobin Han, Jed Ross, Ganesh Kolumam, Min Pi, Junichiro Sonoda, Gwendalyn King, L Darryl Quarles
The bone-derived hormone fibroblast growth factor-23 (FGF-23) activates complexes composed of FGF receptors (FGFRs), including FGFR1, and α-Klotho in the kidney distal tubule (DT), leading to increased sodium retention and hypertension. However, the role of FGFR1 in regulating renal processes linked to hypertension is unclear. Here, we investigated the effects of selective FGFR1 loss in the DT. Conditional knockout (cKO) of FGFR1 in the DT (FGFR1(DT-cKO) mice) resulted in left ventricular hypertrophy (LVH) and decreased kidney expression of α-Klotho in association with enhanced BP, decreased expression of angiotensin converting enzyme 2, and increased expression of the Na(+)-K(+)-2Cl(-) cotransporter...
October 9, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28983729/increased-casr-and-trpc6-pulmonary-vascular-expression-in-the-nitrofen-induced-model-of-congenital-diaphragmatic-hernia
#7
Hiroki Nakamura, Julia Zimmer, Tristan Lim, Prem Puri
AIMS AND OBJECTIVES: The high morbidity and mortality rates in congenital diaphragmatic hernia (CDH) are attributed primarily to severe lung hypoplasia and/or persistent pulmonary hypertension (PPH). PPH in CDH is characterized by abnormal vascular remodeling with thickening of medial and adventitial layers and extension of smooth muscle into previously nonmuscularized arteries. Excessive proliferation of pulmonary arterial smooth muscle cells (PASMC) is an important contributor to the concentric pulmonary arterial remodeling...
October 5, 2017: Pediatric Surgery International
https://www.readbyqxmd.com/read/28982580/stimulation-of-transient-receptor-potential-m3-trpm3-channels-increases-interleukin-8-gene-promoter-activity-involving-ap-1-and-extracellular-signal-regulated-protein-kinase
#8
Sandra Rubil, Andrea Lesch, Naofumi Mukaida, Gerald Thiel
Stimulation of Ca(2+) permeable TRPM3 (transient receptor potential melastatin-3) channels with the steroid ligand pregnenolone sulfate activates stimulus-responsive transcription factors, including the transcription factor AP-1 (activator protein-1). As part of a search for AP-1-regulated target genes we analyzed the gene encoding interleukin-8 (IL-8) in HEK293 cells expressing TRPM3 channels. Here, we show that stimulation of TRPM3 channels activated transcription of an IL-8 promoter-controlled reporter gene that was embedded into the chromatin of the cells...
October 2, 2017: Cytokine
https://www.readbyqxmd.com/read/28957813/nicotine-induced-airway-smooth-muscle-cell-proliferation-involves-trpc6-dependent-calcium-influx-via-%C3%AE-7-nachr
#9
Wei Hong, Gongyong Peng, Binwei Hao, Baoling Liao, Zhuxiang Zhao, Yumin Zhou, Fang Peng, Xiuqin Ye, Lingmei Huang, Mengning Zheng, Jinding Pu, Chunxiao Liang, Erkang Yi, Huanhuan Peng, Bing Li, Pixin Ran
BACKGROUND/AIMS: The proliferation of human bronchial smooth muscle cells (HBSMCs) is a key pathophysiological component of airway remodeling in chronic obstructive pulmonary disease (COPD) for which pharmacotherapy is limited, and only slight improvements in survival have been achieved in recent decades. Cigarette smoke is a well-recognized risk factor for COPD; however, the pathogenesis of cigarette smoke-induced COPD remains incompletely understood. This study aimed to investigate the mechanisms by which nicotine affects HBSMC proliferation...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28921387/analysis-of-24-genes-reveals-a-monogenic-cause-in-11-1-of-cases-with-steroid-resistant-nephrotic-syndrome-at-a-single-center
#10
Weizhen Tan, Svjetlana Lovric, Shazia Ashraf, Jia Rao, David Schapiro, Merlin Airik, Shirlee Shril, Heon Yung Gee, Michelle Baum, Ghaleb Daouk, Michael A Ferguson, Nancy Rodig, Michael J G Somers, Deborah R Stein, Asaf Vivante, Jillian K Warejko, Eugen Widmeier, Friedhelm Hildebrandt
BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) is the second most frequent cause of end-stage renal disease (ESRD) among patients manifesting at under 25 years of age. We performed mutation analysis using a high-throughput PCR-based microfluidic technology in 24 single-gene causes of SRNS in a cohort of 72 families, who presented with SRNS before the age of 25 years. METHODS: Within an 18-month interval, we obtained DNA samples, pedigree information, and clinical information from 77 consecutive children with SRNS from 72 different families seen at Boston Children's Hospital (BCH)...
September 18, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28916337/angiotensin-ii-induces-calcium-mediated-autophagy-in-podocytes-through-enhancing-reactive-oxygen-species-levels
#11
Na Gao, Hui Wang, Hongqiang Yin, Zhuo Yang
As well known, abnormalities of Angiotensin II (Ang II) is closely related with glomerular damage. This study was to investigate whether Ang II could affect autophagy in podocytes via oxidative stress, and whether autophagy had a positive role in protecting podocytes impaired by Ang II. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that Ang II induced podocyte death. The measurements of malondialdehyde (MDA) and H2O2 levels, and flow cytometry assay revealed that Ang II considerably increased reactive oxygen species (ROS) generation in podocytes...
November 1, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28902407/trpc6-expression-in-neurons-is-differentially-regulated-by-nr2a-and-nr2b-containing-nmda-receptors
#12
Zhongwei Qu, Yuqing Wang, Xia Li, Lin Wu, Yizheng Wang
The expression of transient receptor potential canonical 6 (TRPC6) in central nervous system (CNS) is important for neuronal functions and certain neural disorders. However, the regulatory mechanism of TRPC6 expression in neurons is still obscure. In this study, we show that TRPC6 expression in the primary cultured cortical neurons is bidirectionally regulated by glutamate. Activation of NR2A-containing NMDARs induces TRPC6 transcription through a calcineurin-dependent pathway. In contrast, activation of NR2B-containing NMDARs causes TRPC6 degradation through calpain...
November 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28900930/cardiac-remodeling-and-disease-soce-and-trpc-signaling-in-cardiac-pathology
#13
Petra Eder
TRPC channels have been suggested as potential candidates mediating store-operated Ca(2+) 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
https://www.readbyqxmd.com/read/28877958/proline-dependent-and-basophilic-kinases-phosphorylate-human-trpc6-at-serine-14-to-control-channel-activity-through-increased-membrane-expression
#14
Henning Hagmann, Nicole Mangold, Markus M Rinschen, Tim Koenig, Karl Kunzelmann, Bernhard Schermer, Thomas Benzing, Paul T Brinkkoetter
Signaling via the transient receptor potential (TRP) ion channel C6 plays a pivotal role in hereditary and sporadic glomerular kidney disease. Several studies have identified gain-of-function mutations of TRPC6 and report induced expression and enhanced channel activity of TRPC6 in association with glomerular diseases. Interfering with TRPC6 activity may open novel therapeutic pathways. TRPC6 channel activity is controlled by protein expression and stability as well as intracellular trafficking. Identification of regulatory phosphorylation sites in TRPC6 and corresponding protein kinases is essential to understand the regulation of TRPC6 activity and may result in future therapeutic strategies...
September 6, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28839241/leukocyte-trp-channel-gene-expressions-in%C3%A2-patients-with-non-valvular-atrial-fibrillation
#15
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
https://www.readbyqxmd.com/read/28835433/integration-of-trpc6-and-nadph-oxidase-activation-in-lysophosphatidylcholine-induced-trpc5-externalization
#16
Pinaki Chaudhuri, Michael A Rosenbaum, Lutz Birnbaumer, Linda M Graham
Lipid oxidation products, including lysophosphatidylcholine (lysoPC), activate TRPC6, and the subsequent increase in intracellular Ca(2+) 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 p47(phox) and subsequent NADPH oxidase activation with increased production of reactive oxygen species. ERK activation requires TRPC6 opening and influx of Ca(2+) as evidenced by the failure of lysoPC to induce ERK phosphorylation in TRPC6(-/-) endothelial cells...
August 23, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28800680/pharmacological-inhibition-of-focal-segmental-glomerulosclerosis-related-gain-of-function-mutants-of-trpc6-channels-by-semi-synthetic-derivatives-of-larixol
#17
Nicole Urban, Sonja Neuser, Anika Hentschel, Sebastian Köhling, Jörg Rademann, Michael Schaefer
BACKGROUND AND PURPOSE: Gain of function mutations in TRPC6 channels can cause autosomal dominant forms of focal segmental glomerulosclerosis (FSGS). Validated inhibitors of TRPC6 channels that are biologically active on FSGS-related TRPC6 mutants are eagerly sought. EXPERIMENTAL APPROACH: We synthesized new TRPC6-inhibiting modulators from larixol, a resiniferous constituent of Larix decidua, and tested the potency and selectivity in cell lines stably expressing various TRPC channel isoforms...
November 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28790356/trpc6-counteracts-trpc3-nox2-protein-complex-leading-to-attenuation-of-hyperglycemia-induced-heart-failure-in-mice
#18
Sayaka Oda, Takuro Numaga-Tomita, Naoyuki Kitajima, Takashi Toyama, Eri Harada, Tsukasa Shimauchi, Akiyuki Nishimura, Tatsuya Ishikawa, Yoshito Kumagai, Lutz Birnbaumer, Motohiro Nishida
Excess production of reactive oxygen species (ROS) caused by hyperglycemia is a major risk factor for heart failure. We previously reported that transient receptor potential canonical 3 (TRPC3) channel mediates pressure overload-induced maladaptive cardiac fibrosis by forming stably functional complex with NADPH oxidase 2 (Nox2). Although TRPC3 has been long suggested to form hetero-multimer channels with TRPC6 and function as diacylglycerol-activated cation channels coordinately, the role of TRPC6 in heart is still obscure...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28763429/genome-wide-association-study-of-cardiotoxicity-in-the-ncctg-n9831-alliance-adjuvant-trastuzumab-trial
#19
Daniel J Serie, Julia E Crook, Brian M Necela, Travis J Dockter, Xue Wang, Yan W Asmann, DeLisa Fairweather, Katelyn A Bruno, Gerardo Colon-Otero, Edith A Perez, E Aubrey Thompson, Nadine Norton
OBJECTIVES: The major clinical side effect of the ERBB2-targeted breast cancer therapy, trastuzumab, is a decline in the left ventricular ejection fraction (LVEF). Improved markers are needed to better identify patients susceptible to cardiotoxicity. METHODS: The NCCTG N9831 trial compared adjuvant doxorubicin and cyclophosphamide followed by either weekly paclitaxel (arm A); paclitaxel then trastuzumab (arm B); or concurrent paclitaxel and trastuzumab (arm C) in patients with HER2-positive breast cancer...
October 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28756533/long-term-spironolactone-treatment-reduces-coronary-trpc-expression-vasoconstriction-and-atherosclerosis-in-metabolic-syndrome-pigs
#20
Wennan Li, Xingjuan Chen, Ashley M Riley, S Christopher Hiett, Constance J Temm, Eleni Beli, Xin Long, Saikat Chakraborty, Mouhamad Alloosh, Fletcher A White, Maria B Grant, Michael Sturek, Alexander G Obukhov
Coronary transient receptor potential canonical (TRPC) channel expression is elevated in metabolic syndrome (MetS). However, differential contribution of TRPCs to coronary pathology in MetS is not fully elucidated. We investigated the roles of TRPC1 and TRPC6 isoforms in coronary arteries of MetS pigs and determined whether long-term treatment with a mineralocorticoid receptor inhibitor, spironolactone, attenuates coronary TRPC expression and associated dysfunctions. MetS coronary arteries exhibited significant atherosclerosis, endothelial dysfunction, and increased histamine-induced contractions...
September 2017: Basic Research in Cardiology
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