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https://www.readbyqxmd.com/read/29165691/estradiol-protects-proopiomelanocortin-neurons-against-insulin-resistance
#1
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
https://www.readbyqxmd.com/read/29143228/effect-of-exosome-biomarkers-for-diagnosis-and-prognosis-of-breast-cancer-patients
#2
REVIEW
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
https://www.readbyqxmd.com/read/29061651/trpc5-does-not-cause-or-aggravate-glomerular-disease
#3
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
https://www.readbyqxmd.com/read/28978766/trpc5-is-required-for-the-no-dependent-increase-in-dendritic-ca-2-and-gaba-release-from-chick-retinal-amacrine-cells
#4
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
https://www.readbyqxmd.com/read/28900930/cardiac-remodeling-and-disease-soce-and-trpc-signaling-in-cardiac-pathology
#5
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/28864720/overexpression-of-trpc5-promotes-tumor-metastasis-via-the-hif-1%C3%AE-twist-signaling-pathway-in-colon-cancer
#6
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-)
https://www.readbyqxmd.com/read/28839241/leukocyte-trp-channel-gene-expressions-in%C3%A2-patients-with-non-valvular-atrial-fibrillation
#7
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
#8
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/28807145/a-benzothiadiazine-derivative-and-methylprednisolone-are-novel-and-selective-activators-of-transient-receptor-potential-canonical-5-trpc5-channels
#9
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
https://www.readbyqxmd.com/read/28790178/heteromeric-channels-formed-by-trpc1-trpc4-and-trpc5-define-hippocampal-synaptic-transmission-and-working-memory
#10
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
https://www.readbyqxmd.com/read/28675783/insulin-and-leptin-excite-anorexigenic-proopiomelanocortin-neurons-via-activation-of-trpc5-channels
#11
REVIEW
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
https://www.readbyqxmd.com/read/28600513/trpc5-induced-autophagy-promotes-drug-resistance-in-breast-carcinoma-via-camkk%C3%AE-ampk%C3%AE-mtor-pathway
#12
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
https://www.readbyqxmd.com/read/28539583/transient-receptor-potential-canonical-5-channels-plays-an-essential-role-in-hepatic-dyslipidemia-associated-with-cholestasis
#13
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
https://www.readbyqxmd.com/read/28531217/store-operated-ca2-entry-supports-contractile-function-in-hearts-of-hibernators
#14
COMPARATIVE STUDY
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/28522036/transient-receptor-potential-trp-channel-function-in-the-reproductive-axis
#15
REVIEW
Viktoria Götz, Sen Qiao, Andreas Beck, Ulrich Boehm
Transient receptor potential (TRP) channels play important functional roles in the signal transduction machinery of hormone-secreting cells and have recently been implicated in reproductive physiology. While expression studies have demonstrated TRP channel expression at all levels of the hypothalamic-pituitary-gonadal (hpg) axis, functional details about TRP channel action at the level of the individual cells controlling reproduction are just beginning to emerge. Canonical TRP (TRPC) channels are prominently expressed in the reproductive center of the neuroendocrine brain, i...
November 2017: Cell Calcium
https://www.readbyqxmd.com/read/28508318/trpc-channels-and-epilepsy
#16
REVIEW
Fang Zheng
Accumulating evidence suggest that TRPC channels play critical roles in various aspects of epileptogenesis. TRPC1/4 channels are major contributors to nonsynaptically derived epileptiform burst firing in the CA1 and the lateral septum. TRPC7 channels play a critical role in synaptically derived epileptiform burst firing. The reduction of spontaneous epileptiform bursting in the CA3 is correlated to a reduction in pilocarpine-induced SE in vivo in TRPC7 knockout mice. TRPC channels are also significant contributors to SE-induced neuronal cell death...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28325835/picomolar-selective-and-subtype-specific-small-molecule-inhibition-of-trpc1-4-5-channels
#17
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/28324107/functional-characterization-of-transient-receptor-potential-trp-channel-c5-in-female-murine-gonadotropes
#18
Andreas Beck, Viktoria Götz, Sen Qiao, Petra Weissgerber, Veit Flockerzi, Marc Freichel, Ulrich Boehm
Gonadotrope cells in the anterior pituitary gland secrete gonadotropins regulating gonadal function in mammals. Recent results have implicated transient receptor potential (TRP) cation channels in pituitary physiology; however, if and how TRP channels contribute to gonadotrope function is not known. Here, we report that 14 out of 28 TRP channels encoded in the mouse genome are expressed in murine gonadotropes with highest expression levels found for canonical TRP (TRPC) channel 5 in juvenile females. We show that TRP channel expression in these cells exhibits considerable plasticity and that it depends on the sex and the developmental and hormonal status of the animal...
April 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28274093/canonical-transient-receptor-potential-channels-and-their-link-with-cardio-cerebro-vascular-diseases
#19
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 Ca(2+) 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...
September 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28237267/trpc5-channel-modulates-endothelial-cells-senescence
#20
Zhengtao Li, Gang Guo, Hongrui Wang, Xiaoqin Si, Guoli Zhou, Yong Xiong, Sujuan Li, Rong Dai, Cui Yang
As a Ca(2+)-permeable cationic channel, canonical transient receptor potential 5 channel (TRPC5) has been known to be involved in various functions of cells. Although TRPC5 is abundantly expressed in vascular endothelium, it remains unknown whether TRPC5 plays a role in regulating endothelial senescence. In the present study, we investigated the involvement of TRPC5 in the senescence of mouse aortic endothelial cells (MAECs). Meanwhile, the regulatory role of TRPC5 in the endothelial dysfunction in aged mice was also studied...
May 5, 2017: European Journal of Pharmacology
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