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https://www.readbyqxmd.com/read/28540409/angiotensin-ii-induces-calcium-calcineurin-signaling-and-podocyte-injury-by-downregulating-microrna-30-family-members
#1
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...
May 24, 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
#2
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
#3
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
#4
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
#5
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...
May 8, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28479396/trpc6-mediated-erk1-2-phosphorylation-prevents-dentate-granule-cell-degeneration-via-inhibiting-mitochondrial-elongation
#6
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...
May 4, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28476686/mutation-spectrum-of-genes-associated-with-steroid-resistant-nephrotic-syndrome-in-chinese-children
#7
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...
May 2, 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
#8
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
https://www.readbyqxmd.com/read/28442546/modeled-structural-basis-for-the-recognition-of-%C3%AE-2-3-sialyllactose-by-soluble-klotho
#9
Jon D Wright, Sung-Wan An, Jian Xie, Joonho Yoon, Nicole Nischan, Jennifer J Kohler, Noelynn Oliver, Carmay Lim, Chou-Long Huang
Soluble Klotho (sKlotho) is the shed ectodomain of antiaging membrane Klotho that contains 2 extracellular domains KL1 and KL2, each of which shares sequence homology to glycosyl hydrolases. sKlotho elicits pleiotropic cellular responses with a poorly understood mechanism of actions. Notably, in injury settings, sKlotho confers cardiac and renal protection by down-regulating calcium-permeable transient receptor potential canonical type isoform 6 (TRPC6) channels in cardiomyocytes and glomerular podocytes. Inhibition of PI3K-dependent exocytosis of TRPC6 is thought to be the underlying mechanism, and recent studies showed that sKlotho interacts with α2-3-sialyllactose-containing gangliosides enriched in lipid rafts to inhibit raft-dependent PI3K signaling...
April 25, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28430879/role-of-phosphatase-and-tensin-homolog-pten-in-hypoxic-pulmonary-vasoconstriction
#10
Adrienn Krauszman, Tak Mak, Katalin Szaszi, Wolfgang M Kuebler
AIMS: Hypoxic pulmonary vasoconstriction (HPV) redistributes blood flow from poorly ventilated to better aerated areas in the lung, thereby optimizing ventilation-perfusion ratio (V/Q). Pulmonary artery smooth muscle cell (PASMC) contraction in response to hypoxia is triggered by Ca2+ influx via transient receptor potential canonical 6 (TRPC6) cation channels that have translocated to caveolae in the plasma membrane. Since phosphatase and tensin homolog (PTEN) was suggested to regulate TRPC6 in endothelial cells, we aimed to define its role in the hypoxic response of PASMCs and as a putative mediator of HPV...
April 18, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28430609/characterization-of-pressure-mediated-vascular-tone-in-resistance-arteries-from-bile-duct-ligated-rats
#11
Ravirajsinh N Jadeja, Menaka C Thounaojam, Sandeep Khurana
In cirrhosis, changes in pressure-mediated vascular tone, a key determinant of systemic vascular resistance (SVR), are unknown. To address this gap in knowledge, we assessed ex vivo dynamics of pressurized mesenteric resistance arteries (diameter ~ 260 μm) from bile duct-ligated (BDL) and sham-operated (SHAM) rats and determined the underlying mechanisms. At isobaric intraluminal pressure (70 mmHg) as well as with step-wise increase in pressure (10-110 mmHg), arteries from SHAM-rats constricted more than BDL-rats, and had reduced luminal area...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416610/evidence-for-shear-mediated-ca-2-entry-through-mechanosensitive-cation-channels-in-human-platelets-and-a-megakaryocytic-cell-line
#12
Zeki Ilkan, Joy R Wright, Alison H Goodall, Jonathan M Gibbins, Chris I Jones, Martyn P Mahaut-Smith
The role of mechanosensitive (MS) Ca(2+)-permeable ion channels in platelets is unclear, despite the importance of shear stress in platelet function and life-threatening thrombus formation. We therefore sought to investigate the expression and functional relevance of MS channels in human platelets. The effect of shear stress on Ca(2+) entry in human platelets and Meg-01 megakaryocytic cells loaded with Fluo-3 was examined by confocal microscopy. Cells were attached to microscope slides within flow chambers that allowed applications of physiological and pathological shear stress...
April 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28400714/deletion-of-trpc6-attenuates-nmda-receptor-mediated-ca-2-entry-and-ca-2-induced-neurotoxicity-following-cerebral-ischemia-and-oxygen-glucose-deprivation
#13
Jin Chen, Zhaozhong Li, Jeffery T Hatcher, Qing-Hui Chen, Li Chen, Robert D Wurster, Sic L Chan, Zixi Cheng
Transient receptor potential canonical 6 (TRPC6) channels are permeable to Na(+) and Ca(2+) and are widely expressed in the brain. In this study, the role of TRPC6 was investigated following ischemia/reperfusion (I/R) and oxygen-glucose deprivation (OGD). We found that TRPC6 expression was increased in wild-type (WT) mice cortical neurons following I/R and in primary neurons with OGD, and that deletion of TRPC6 reduced the I/R-induced brain infarct in mice and the OGD- /neurotoxin-induced neuronal death. Using live-cell imaging to examine intracellular Ca(2+) levels ([Ca(2+)] i ), we found that OGD induced a significant higher increase in glutamate-evoked Ca(2+) influx compared to untreated control and such an increase was reduced by TRPC6 deletion...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28395140/pyrazolopyrimidines-as-potent-stimulators-for-transient-receptor-potential-canonical-3-6-7-channels
#14
Chunrong Qu, Mingmin Ding, Yingmin Zhu, Yungang Lu, Juan Du, Melissa Miller, Jinbin Tian, Jinmei Zhu, Jian Xu, Meng Wen, Aga Er-Bu, Jule Wang, Yuling Xiao, Meng Wu, Owen B McManus, Min Li, Jilin Wu, Huai-Rong Luo, Zhengyu Cao, Bing Shen, Hongbo Wang, Michael X Zhu, Xuechuan Hong
Transient receptor potential canonical 3/6/7 (TRPC3/6/7) are highly homologous receptor-operated nonselective cation channels. Despite their physiological significance, very few selective and potent agonists are available for functional examination of these channels. Using a cell-based high throughput screening approach, a lead compound with the pyrazolopyrimidine skeleton was identified as a TRPC6 agonist. Synthetic schemes for the lead and its analogues were established, and structural-activity relationship studies were carried out...
April 28, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28331185/the-role-of-angiotensin-ii-in-glomerular-volume-dynamics-and-podocyte-calcium-handling
#15
Daria V Ilatovskaya, Oleg Palygin, Vladislav Levchenko, Bradley T Endres, Alexander Staruschenko
Podocytes are becoming a primary focus of research efforts due to their association with progressive glomeruli damage in disease states. Loss of podocytes can occur as a result of excessive intracellular calcium influx, and we have previously shown that angiotensin II (Ang II) via canonical transient receptor potential 6 (TRPC6) channels caused increased intracellular Ca(2+) flux in podocytes. We showed here with patch-clamp electrophysiology that Ang II activates TRPC channels; then using confocal calcium imaging we demonstrated that Ang II-dependent stimulation of Ca(2+) influx in the podocytes is precluded by blocking either AT1 or AT2 receptors (ATRs)...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28325835/picomolar-selective-and-subtype-specific-small-molecule-inhibition-of-trpc1-4-5-channels
#16
Hussein N Rubaiy, Melanie J Ludlow, Matthias Henrot, Hannah J Gaunt, Katarina Miteva, Sin Ying 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...
May 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28314576/trpc6-and-kidney-disease-sclerosing-more-than-just-glomeruli
#17
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
#18
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...
June 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
#19
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
#20
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
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