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https://www.readbyqxmd.com/read/28729555/inhibition-of-phosphodiesterase-5-suppresses-calcineurin-nfat-mediated-trpc6-expression-in-pulmonary-artery-smooth-muscle-cells
#1
Shaojun Li, Yilin Pan, Rui Ke, Xinming Xie, Cui Zhai, Wenhua Shi, Jian Wang, Xin Yan, Limin Chai, Qingting Wang, Qianqian Zhang, Xiaofan Su, Lan Yang, Li Gao, Manxiang Li
The up-regulation of transient receptor potential channel 6 (TRPC6) has been found to contribute to the proliferation of pulmonary artery smooth muscle cells (PASMCs), and inhibition of phosphodiesterase-5 (PDE5) has been shown to suppress TRPC6 expression in PASMCs. However, the molecular mechanisms underlying the up-regulation of TRPC6 expression and PDE5 modulation of TRPC6 expression in PASMCs remain largely unclear. The aim of this study is to address these issues. Endothelin-1 (ET-1) dose and time-dependently up-regulated TRPC6 expression in primary cultured rat PASMCs, and this was accompanied with the activation of calcineurin and subsequent translocation of NFATc4 to the nucleus...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28696436/reduced-trpc6-mrna-levels-in-the-blood-cells-of-patients-with-alzheimer-s-disease-and-mild-cognitive-impairment
#2
R Lu, J Wang, R Tao, J Wang, T Zhu, W Guo, Y Sun, H Li, Y Gao, W Zhang, C J Fowler, Q Li, S Chen, Z Wu, C L Masters, C Zhong, N Jing, Y Wang, Y Wang
Transient receptor potential canonical 6 (TRPC6) inhibits β-amyloid (Aβ) production. Hyperforin, the TRPC6 agonist, reduces Aβ levels and improves cognitive performance in Alzheimer's disease (AD) models. However, it's unknown whether TRPC6 expression is changed in AD patients. In this case-control study, we measured TRPC6 expression levels in the peripheral blood cells of four independent AD sets from five hospitals and one mild cognitive impairment (MCI) set from a local community (229 AD, 70 MCI, 40 Parkinson disease and 359 controls from China, total n=698) using quantitative real-time PCR assay...
July 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28687864/stressed-podocytes-mechanical-forces-sensors-signaling-and-response
#3
REVIEW
Karlhans Endlich, Felix Kliewe, Nicole Endlich
Increased glomerular capillary pressure (glomerular hypertension) and increased glomerular filtration rate (glomerular hyperfiltration) have been proven to cause glomerulosclerosis in animal models and are likely to be operative in patients. Since podocytes cover the glomerular basement membrane, they are exposed to tensile stress due to circumferential wall tension and to fluid shear stress arising from filtrate flow through the narrow filtration slits and through Bowman's space. In vitro evidence documents that podocytes respond to tensile stress as well as to fluid shear stress...
July 7, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28672895/role-of-transient-receptor-potential-channel-6-in-the-odontogenic-differentiation-of-human-dental-pulp-cells
#4
Xiaoting Yang, Zhi Song, Lingling Chen, Runfu Wang, Shuheng Huang, Wei Qin, Jia Guo, Zhengmei Lin
Pulp capping is a restorative technique employed in an attempt to maintain pulpal vitality and generate reparative dentin. Ca(2+) released from capping materials is suggested to promote reparative dentin formation. Transient receptor potential channel 6 (TRPC6) is a receptor-operated Ca2+ channel that serves an important role in Ca2+ influx in the majority of non-excitable cells, and influences the calcium signaling and cell respond. Therefore, the purpose of the present study was to gain an insight into the role of TRPC6 in the odontoblastic differentiation of human dental pulp cells (HDPCs)...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28670316/the-role-of-transient-receptor-potential-channel-6-channels-in-the-pulmonary-vasculature
#5
REVIEW
Monika Malczyk, Alexandra Erb, Christine Veith, Hossein Ardeschir Ghofrani, Ralph T Schermuly, Thomas Gudermann, Alexander Dietrich, Norbert Weissmann, Akylbek Sydykov
Canonical or classical transient receptor potential channel 6 (TRPC6) is a Ca(2+)-permeable non-selective cation channel that is widely expressed in the heart, lung, and vascular tissues. The use of TRPC6-deficient ("knockout") mice has provided important insights into the role of TRPC6 in normal physiology and disease states of the pulmonary vasculature. Evidence indicates that TRPC6 is a key regulator of acute hypoxic pulmonary vasoconstriction. Moreover, several studies implicated TRPC6 in the pathogenesis of pulmonary hypertension...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28646178/increased-glomerular-filtration-rate-and-impaired-contractile-function-of-mesangial-cells-in-trpc6-knockout-mice
#6
Weizu Li, Yanfeng Ding, Crystal Smedley, Yanxia Wang, Sarika Chaudhari, Lutz Birnbaumer, Rong Ma
The present study was conducted to determine if TRPC6 regulates glomerular filtration rate (GFR) and the contractile function of glomerular mesangial cells (MCs). GFR was assessed in conscious TRPC6 wild type and knockout mice, and in anesthetized rats with and without in vivo knockdown of TRPC6 in kidneys. We found that GFR was significantly greater, and serum creatinine level was significantly lower in TRPC6 deficient mice. Consistently, local knockdown of TRPC6 in kidney using TRPC6 specific shRNA construct significantly attenuated Ang II-induced GFR decline in rats...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28645743/role-of-trpc3-and-trpc6-channels-in-the-myocardial-response-to-stretch-linking-physiology-and-pathophysiology
#7
REVIEW
Yohei Yamaguchi, Gentaro Iribe, Motohiro Nishida, Keiji Naruse
Transient receptor potential (TRP) channels constitute a large family of versatile multi-signal transducers. In particular, TRP canonical (TRPC) channels are known as receptor-operated, non-selective cation channels. TRPC3 and TRPC6, two members in the TRPC family, are highly expressed in the heart, and participate in the pathogenesis of cardiac hypertrophy and heart failure as a pathological response to chronic mechanical stress. In the pathological response, myocardial stretch increases intracellular Ca(2+) levels and activates nuclear factor of activated T cells to induce cardiac hypertrophy...
June 20, 2017: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/28629718/changes-in-podocyte-trpc-channels-evoked-by-plasma-and-sera-from-patients-with-recurrent-fsgs-and-by-putative-glomerular-permeability-factors
#8
Eun Young Kim, Hila Roshanravan, Stuart E Dryer
Primary forms of focal and segmental glomerulosclerosis (FSGS) are driven by circulating factors that cause dysfunction or loss podocytes. Rare genetic forms of FSGS can be caused by mutations in TRPC6, which encodes a Ca(2+)-permeable cationic channel expressed in mesangial cells and podocytes; and NPHS2, which encodes podocin, a TRPC6-binding protein expressed in podocyte slit diaphragm domains. Here we observed that exposing immortalized mouse podocytes to serum or plasma from recurrent FSGS patients for 24h increased the steady-state cell-surface abundance of TRPC6, accompanied by an increase in currents through endogenous TRPC6 channels evoked by a hypoosmotic stretch stimulus...
June 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28627661/altered-expression-of-ppar%C3%A2-%C3%AE-and-trpc-in-neonatal-rats-with-persistent-pulmonary-hypertension
#9
Yanna Du, Jianhua Fu, Li Yao, Lin Qiao, Na Liu, Yujiao Xing, Xindong Xue
Persistent pulmonary hypertension of the newborn (PPHN) is a life‑threatening disease that is commonly observed in the neonatal intensive care unit. PPHN is pathologically characterized by pulmonary vascular remodeling and, in particular, pulmonary artery smooth muscle cell (PASMC) proliferation. Decreased expression levels of peroxisome proliferator‑activated receptor γ (PPAR‑γ), which is a member of the nuclear receptor hormone superfamily, in combination with elevated expressions of transient receptor potential cation channel, subfamily C, member 1 (TRPC1) and TRPC6 contributes to the PASMC proliferation and excessive pulmonary vascular remodeling in adult pulmonary hypertension (PH)...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28596571/the-role-of-trpc6-in-the-neuroprotection-of-calycosin-against-cerebral-ischemic-injury
#10
Chao Guo, Yongyuan Ma, Shanbo Ma, Fei Mu, Jiao Deng, Jialin Duan, Lize Xiong, Ying Yin, Yanhua Wang, Miaomaio Xi, Aidong Wen
Our previous studies have provided evidences that calycosin can protect the brain from ischemia/reperfusion injury, but its mechanisms is not fully understand. Transient receptor potential canonical 6 (TRPC6) has a critical role in promoting neuronal survival against cerebral ischemic injury. The aim of the present study is to test whether calycosin protects against cerebral ischemic injury through TRPC6-CREB pathway. In vivo, rats were subjected to transient middle cerebral artery occlusion (MCAO) for 2 h and then treated with different doses of calycosin at the onset of reperfusion...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28580132/case-report-making-a-diagnosis-of-familial-renal-disease-clinical-and-patient-perspectives
#11
Zahra Iqbal, John A Sayer
BACKGROUND: A precise molecular genetic diagnosis has become the gold standard for the correct identification and management of many inherited renal diseases. METHODS: Here we describe a family with familial focal segmental glomerulosclerosis, and include a clinical and patient perspective on the diagnostic workup and relaying of genetic results following whole exome sequencing. RESULTS: Through next generation sequencing approaches, we identified a pathogenic mutation in TRPC6, the underlying cause of the phenotype...
2017: F1000Research
https://www.readbyqxmd.com/read/28566634/effect-of-docosahexaenoic-acid-on-voltage-independent-ca-2-entry-pathways-in-cultured-vascular-smooth-muscle-cells-stimulated-with-5-hydroxytryptamine
#12
Takuji Machida, Akina Onoguchi, Kenji Iizuka, Sayuri Ishibashi, Mikiko Yutani, Masahiko Hirafuji
We previously reported that docosahexaenoic acid (DHA) inhibits an increase in intracellular Ca(2+) concentration ([Ca(2+)]i) in cultured rat vascular smooth muscle cells (VSMCs) through a mechanism involving mainly voltage-dependent Ca(2+) channels; however, the effect of DHA on voltage-independent pathways, such as store-operated and receptor-operated Ca(2+) entry, and Ca(2+) entry through Na(+)/Ca(2+) exchanger (NCX), has not been clarified. In the present study, we investigated the effect of DHA treatment on the expression of transient receptor potential canonical (TRPC) channels, capacitative Ca(2+) entry, and Ca(2+) entry through NCX in rat cultured VSMCs stimulated with 5-hydroxytryptamine (5-HT)...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28540409/angiotensin-ii-induces-calcium-calcineurin-signaling-and-podocyte-injury-by-downregulating-microrna-30-family-members
#13
Yue Zhao, Junnan Wu, Mingchao Zhang, Minlin Zhou, Feng Xu, Xiaodong Zhu, Xianguang Zhou, Yue Lang, Fan Yang, Shifeng Yun, Shaolin Shi, Zhihong Liu
Angiotensin II (AngII) is capable of inducing calcium/calcineurin signaling and podocyte injury; however, the precise underlying mechanism is not well understood. Because we have previously demonstrated that microRNA-30s (miR-30s) inhibit calcium/calcineurin signaling in podocytes, we hypothesize that AngII may induce podocyte injury by downregulating miR-30s and thereby activating calcium/calcineurin signaling. To test this hypothesis, we used an AngII-induced podocyte injury mouse model. The mice were treated with AngII via infusion for 28 days, which resulted in hypertension, albuminuria, and glomerular damage...
August 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28531217/store-operated-ca2-entry-supports-contractile-function-in-hearts-of-hibernators
#14
Olga V Nakipova, Alexey S Averin, Edward V Evdokimovskii, Oleg Yu Pimenov, Leonid Kosarski, Dmitriy Ignat'ev, Andrey Anufriev, Yuri M Kokoz, Santiago Reyes, Andre Terzic, Alexey E Alekseev
Hibernators have a distinctive ability to adapt to seasonal changes of body temperature in a range between 37°C and near freezing, exhibiting, among other features, a unique reversibility of cardiac contractility. The adaptation of myocardial contractility in hibernation state relies on alterations of excitation contraction coupling, which becomes less-dependent from extracellular Ca2+ entry and is predominantly controlled by Ca2+ release from sarcoplasmic reticulum, replenished by the Ca2+-ATPase (SERCA)...
2017: PloS One
https://www.readbyqxmd.com/read/28508314/trpc-channels-and-alzheimer-s-disease
#15
Rui Lu, Qian He, Junfeng Wang
Alzheimer's disease (AD) is the most common neurodegenerative disease in the world. The "amyloid hypothesis" is one of the predominant hypotheses for the pathogenesis of AD. Besides, tau protein accumulation, calcium homeostasis disruption, and glial cell activation are also remarkable features in AD. Recently, there are some reports showing that TRPC channels may function in AD development, especially TRPC6. In this chapter, we will discuss the evidence for the involvement of TRPC channels in Alzheimer's disease and the potential of therapeutics for AD based on TRPC channels...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28499580/transient-receptor-potential-trp-channels-as-molecular-targets-in-lung-toxicology-and-associated-diseases
#16
REVIEW
Alexander Dietrich, Dirk Steinritz, Thomas Gudermann
The lungs as the gateways of our body to the external environment are essential for gas exchange. They are also exposed to toxicants from two sides, the airways and the vasculature. Apart from naturally produced toxic agents, millions of human made chemicals were produced since the beginning of the industrial revolution whose toxicity still needs to be determined. While the knowledge about toxic substances is increasing only slowly, a paradigm shift regarding the proposed mechanisms of toxicity at the plasma membrane emerged...
April 26, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28495616/salvianolic-acid-b-attenuates-doxorubicin-induced-er-stress-by-inhibiting-trpc3-and-trpc6-mediated-ca-2-overload-in-rat-cardiomyocytes
#17
Rong-Chang Chen, Gui-Bo Sun, Jing-Xue Ye, Jian Wang, Miao-di Zhang, Xiao-Bo Sun
Doxorubicin (DOX)-induced cardiotoxicity is a clinically complex syndrome that leads to significant pain to cancer survivors. Endoplasmic reticulum (ER) stress has been suggested to be an important contributor to myocardium dysfunction during this phenomenon. Our previous study proved that Salvianolic acid B (Sal B) protected against doxorubicin induced cardiac dysfunction by inhibiting ER stress and cardiomyocyte apoptosis. However, the underlying molecular mechanism is not yet clearly. In this study, we investigated the protective effect and mechanisms of Sal B againest DOX-induced cardiac injury and ER stress in vivo and in vitro...
July 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28479396/trpc6-mediated-erk1-2-phosphorylation-prevents-dentate-granule-cell-degeneration-via-inhibiting-mitochondrial-elongation
#18
Ah-Reum Ko, Tae-Cheon Kang
Transient receptor potential canonical channel-6 (TRPC6) is one of Ca(2+)-permeable non-selective cation channels. In the rat hippocampus, TRPC6 expression is predominantly observed in dentate granule cells (DGC) rather than other hippocampal components. Interestingly, TRPC6 knockdown results in the massive DGC degeneration following status epilepticus (SE), although DGC is one of the resistant neuronal populations to various harmful stresses. However, the molecular events underlying the DGC degeneration induced by TRPC6 knockdown are still unclear...
July 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28476686/mutation-spectrum-of-genes-associated-with-steroid-resistant-nephrotic-syndrome-in-chinese-children
#19
Ying Wang, Xiqiang Dang, Qingnan He, Yan Zhen, Xiaoxie He, Zhuwen Yi, Kuichun Zhu
Approximately 20% of children with idiopathic nephrotic syndrome do not respond to steroid therapy. More than 30 genes have been identified as disease-causing genes for the steroid-resistant nephrotic syndrome (SRNS). Few reports were from the Chinese population. The coding regions of genes commonly associated with SRNS were analyzed to characterize the gene mutation spectrum in children with SRNS in central China. The first phase study involved 38 children with five genes (NPHS1, NPHS2, PLCE1, WT1, and TRPC6) by Sanger sequencing...
August 20, 2017: Gene
https://www.readbyqxmd.com/read/28458019/nf-%C3%AE%C2%BAb-dependent-up-regulation-of-trpc6-by-a%C3%AE-in-bv-2-microglia-cells-increases-cox-2-expression-and-contributes-to-hippocampus-neuron-damage
#20
Na Liu, Yuansu Zhuang, Zhikui Zhou, Jinhua Zhao, Qiaoyun Chen, Jinxu Zheng
The deposition of amyloid β-protein (Aβ) has been involved in neurodegeneration of Alzheimer's disease (AD). Besides Aβ plaques and neuronal loss, microglia activation is also common in AD patient brains, suggesting its important role in the pathogenesis of AD. Although activation of microglia by Aβ plaques has been demonstrated, the mechanism underlying it is still largely unclear. Here, we found that TRPC6 has a crucial role in microglia activation by Aβ. Aβ up-regulates the level of TRPC6 via NF-κB in BV-2 microglia and increases the expression of pro-inflammatory factors and oxidative enzyme, COX-2...
April 27, 2017: Neuroscience Letters
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