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https://www.readbyqxmd.com/read/28807145/a-benzothiadiazine-derivative-and-methylprednisolone-are-novel-and-selective-activators-of-transient-receptor-potential-canonical-5-trpc5-channels
#1
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/28791397/trpc1-stimulates-calcium%C3%A2-sensing-receptor%C3%A2-induced-store%C3%A2-operated-ca2-entry-and-nitric-oxide-production-in-endothelial-cells
#2
Yuan-Yuan Qu, La-Mei Wang, Hua Zhong, Yong-Min Liu, Na Tang, Li-Ping Zhu, Fang He, Qing-Hua Hu
Store‑operated Ca2+ entry (SOCE) via store‑operated Ca2+ channels (SOCC), encoded by transient receptor potential canonical (TRPC) channel proteins, is an important underlying mechanism regulating intracellular Ca2+ concentration ([Ca2+]i) and various intracellular functions in endothelial cells (ECs). TRPC1, the probable candidate for SOCC, is expressed in ECs. Ca2+‑sensing receptor (CaSR) is functionally expressed in vascular endothelium and is important in Ca2+ mobilization and cardiovascular functions...
August 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28790178/heteromeric-channels-formed-by-trpc1-trpc4-and-trpc5-define-hippocampal-synaptic-transmission-and-working-memory
#3
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...
August 8, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28779972/critical-role-of-trpc1-in-thyroid-hormone-dependent-dopaminergic-neuron-development
#4
Chunhai Chen, Qinglong Ma, Ping Deng, Jianjing Yang, Lingling Yang, Min Lin, Zhengping Yu, Zhou Zhou
Thyroid hormones play a crucial role in midbrain dopaminergic (DA) neuron development. However, the underlying molecular mechanisms remain largely unknown. In this study, we revealed that thyroid hormone treatment evokes significant calcium entry through canonical transient receptor potential (TRPC) channels in ventral midbrain neural stem cells and this calcium signaling is essential for thyroid hormone-dependent DA neuronal differentiation. We also found that TRPC1 is the dominant TRPC channel expressed in ventral midbrain neural stem cells which responds to thyroid hormone...
August 2, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28775294/anti-allergic-activity-of-glycyrrhizic-acid-on-ige-mediated-allergic-reaction-by-regulation-of-allergy-related-immune-cells
#5
Shiwen Han, Lu Sun, Feng He, Huilian Che
Glycyrrhizic acid (GA), the major bioactive triterpene glycoside of glycyrrhiza, has been shown to possess a wide range of pharmacological properties, including anti-inflammatory and anti-viral properties. However, few studies have examined the anti-allergic activity and exact mechanism of action of GA. In the present work, the anti-allergic activity and possible mechanisms of action of GA on an immunoglobulin (Ig) E-mediated allergic reaction has been studied using three models of allergic reaction in vivo and in vitro...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28756533/long-term-spironolactone-treatment-reduces-coronary-trpc-expression-vasoconstriction-and-atherosclerosis-in-metabolic-syndrome-pigs
#6
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
https://www.readbyqxmd.com/read/28728119/nf-%C3%AE%C2%BAb-mediated-inflammation-correlates-with-calcium-overload-under-arsenic-trioxide-induced-myocardial-damage-in-gallus-gallus
#7
Siwen Li, Yu Wang, Hongjing Zhao, Ying He, Jinglun Li, Guangshun Jiang, Mingwei Xing
Arsenic is a known environmental pollutant and highly hazardous toxin to human health. Due to the biological accumulation, arsenic produces a variety of cardiovascular diseases. However, the exact mechanism is still unclear. Here, our objective was to evaluate myocardial damage and determine the potential mechanism under arsenic exposure in chickens. Arsenic trioxide (As2O3) (1.25 mg/kg BW, corresponding 15 mg/kg feed) was administered as basal diet to male Hy-line chickens (one-day-old) for 4, 8 and 12 weeks...
October 2017: Chemosphere
https://www.readbyqxmd.com/read/28697491/trpc1-trpc3-and-trpc4-in-rat-orofacial-structures
#8
Masatoshi Fujita, Tadasu Sato, Takehiro Yajima, Eiji Masaki, Hiroyuki Ichikawa
TRPC (transient receptor potential cation channel subfamily C) members are nonselective monovalent cation channels and control Ca2+ inflow. In this study, immunohistochemistry for TRPC1, TRPC3, and TRPC4 was performed on rat oral and craniofacial structures to elucidate their distribution and function in the peripheries. In the trigeminal ganglion (TG), 56.1, 84.1, and 68.3% of sensory neurons were immunoreactive (IR) for TRPC1, TRPC3, and TRPC4, respectively. A double immunofluorescence method revealed that small to medium-sized TG neurons co-expressed TRPCs and calcitonin gene-related peptide...
July 12, 2017: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/28672825/maitotoxin-is-a-potential-selective-activator-of-the-endogenous-transient-receptor-potential-canonical-type-1-channel-in-xenopus-laevis-oocytes
#9
Pedro L Flores, Emma Rodríguez, Estrella Zapata, Roxana Carbó, José María Farías, Martín Martínez
Maitotoxin (MTX) is the most potent marine toxin known to date. It is responsible for a particular human intoxication syndrome called ciguatera fish poisoning (CFP). Several reports indicate that MTX is an activator of non-selective cation channels (NSCC) in different cell types. The molecular identity of these channels is still an unresolved topic, and it has been proposed that the transient receptor potential (TRP) channels are involved in this effect. In Xenopus laevis oocytes, MTX at picomolar (pM) concentrations induces the activation of NSCC with functional and pharmacological properties that resemble the activity of TRP channels...
June 25, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28646178/increased-glomerular-filtration-rate-and-impaired-contractile-function-of-mesangial-cells-in-trpc6-knockout-mice
#10
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/28636132/trpc1-and-trpc3-dependent-ca-2-signaling-in-mouse-cortical-astrocytes-affects-injury-evoked-astrogliosis-in-vivo
#11
Thabet Belkacemi, Alexander Niermann, Laura Hofmann, Ulrich Wissenbach, Lutz Birnbaumer, Petra Leidinger, Christina Backes, Eckart Meese, Andreas Keller, Xianshu Bai, Anja Scheller, Frank Kirchhoff, Stephan E Philipp, Petra Weissgerber, Veit Flockerzi, Andreas Beck
Following brain injury astrocytes change into a reactive state, proliferate and grow into the site of lesion, a process called astrogliosis, initiated and regulated by changes in cytoplasmic Ca(2+) . Transient receptor potential canonical (TRPC) channels may contribute to Ca(2+) influx but their presence and possible function in astrocytes is not known. By RT-PCR and RNA sequencing we identified transcripts of Trpc1, Trpc2, Trpc3, and Trpc4 in FACS-sorted glutamate aspartate transporter (GLAST)-positive cultured mouse cortical astrocytes and subcloned full-length Trpc1 and Trpc3 cDNAs from these cells...
September 2017: Glia
https://www.readbyqxmd.com/read/28629808/physiological-and-pathophysiological-role-of-transient-receptor-potential-canonical-channels-in-cardiac-myocytes
#12
REVIEW
Azmi A Ahmad, Molly Streiff, Chris Hunter, Qinghua Hu, Frank B Sachse
Transient receptor potential canonical (TRPC) channels constitute a family of seven Ca(2+) permeable ion channels, named TRPC1 to 7. These channels are abundantly expressed in the mammalian heart, yet mechanisms underlying activation of TRPC channels and their precise role in cardiac physiology remain poorly understood. In this review, we perused original literature regarding TRPC channels in cardiomyocytes. We first reviewed studies on TRPC channel assembly and sub-cellular localization across multiple species and cell types...
June 16, 2017: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/28627661/altered-expression-of-ppar%C3%A2-%C3%AE-and-trpc-in-neonatal-rats-with-persistent-pulmonary-hypertension
#13
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/28583863/increasing-extracellular-ca-2-sensitizes-tnf-alpha-induced-vascular-cell-adhesion-molecule-1-vcam-1-via-a-trpc1-erk1-2-nf%C3%AE%C2%BAb-dependent-pathway-in-human-vascular-endothelial-cells
#14
Songtao Li, Hua Ning, Yaxin Ye, Wei Wei, Rui Guo, Qing Song, Lei Liu, Yunyun Liu, Lixin Na, Yuchun Niu, Xia Chu, Rennan Feng, Naima Moustaid-Moussa, Ying Li, Changhao Sun
Increasing circulating Ca(2+) levels within the normal range has been reported to positively correlate with the incidence of fatal cardiovascular diseases (CVDs). However, limited studies have been able to delineate the potential mechanism(s) linking circulating Ca(2+) to CVD. In this study, we exposed primary human umbilical vein endothelial cells (HUVECs) and human umbilical vein cell line (EA.hy926) to different extracellular Ca(2+) to mimic the physiological state. Our data revealed that increasing extracellular Ca(2+) significantly enhanced susceptibility to tumor necrosis factor (TNF)-alpha-stimulated vascular cell adhesion molecule (VCAM)-1 expression and monocytes adhesion...
June 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28578393/mti-101-treatment-inducing-activation-of-stim1-and-trpc1-expression-is-a-determinant-of-response-in-multiple-myeloma
#15
Michael F Emmons, Nagaraju Anreddy, Javier Cuevas, Kayla Steinberger, Shengyu Yang, Mark McLaughlin, Ariosto Silva, Lori A Hazlehurst
The emergence of drug resistance continues to be a major hurdle towards improving patient outcomes for the treatment of Multiple Myeloma. MTI-101 is a first-in-class peptidomimetic that binds a CD44/ITGA4 containing complex and triggers necrotic cell death in multiple myeloma cell lines. In this report, we show that acquisition of resistance to MTI-101 correlates with changes in expression of genes predicted to attenuate Ca(2+) flux. Consistent with the acquired resistant genotype, MTI-101 treatment induces a rapid and robust increase in intracellular Ca(2+) levels in the parental cells; a finding that was attenuated in the acquired drug resistant cell line...
June 2, 2017: Scientific Reports
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
#16
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/28559303/trpc1-is-a-differential-regulator-of-hypoxia-mediated-events-and-akt-signalling-in-pten-deficient-breast-cancer-cells
#17
Iman Azimi, Michael J G Milevskiy, Elke Kaemmerer, Dane Turner, Kunsala T D S Yapa, Melissa A Brown, Erik W Thompson, Sarah J Roberts-Thomson, Gregory R Monteith
Hypoxia is a feature of the tumour microenvironment that promotes invasiveness, resistance to chemotherapeutics and cell survival. Our studies identify the transient receptor potential canonical-1 (TRPC1) ion channel as a key component of responses to hypoxia in breast cancer cells. This regulation includes control of specific epithelial to mesenchymal transition (EMT) events and hypoxia-mediated activation of signalling pathways such as activation of the EGFR, STAT3 and the autophagy marker LC3B, through hypoxia-inducible factor-1α (HIF1α)-dependent and -independent mechanisms...
July 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28545724/the-role-of-ca-2-in-cell-death-caused-by-oxidative-glutamate-toxicity-and-ferroptosis
#18
REVIEW
Pamela Maher, Klaus van Leyen, Partha Narayan Dey, Birgit Honrath, Amalia Dolga, Axel Methner
Ca(2+) ions play a fundamental role in cell death mediated by oxidative glutamate toxicity or oxytosis, a form of programmed cell death similar and possibly identical to other forms of cell death like ferroptosis. Ca(2+) influx from the extracellular space occurs late in a cascade characterized by depletion of the intracellular antioxidant glutathione, increases in cytosolic reactive oxygen species and mitochondrial dysfunction. Here, we aim to compare oxidative glutamate toxicity with ferroptosis, address the signaling pathways that culminate in Ca(2+) influx and cell death and discuss the proteins that mediate this...
May 12, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28531217/store-operated-ca2-entry-supports-contractile-function-in-hearts-of-hibernators
#19
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/28508318/trpc-channels-and-epilepsy
#20
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
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