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https://www.readbyqxmd.com/read/29896230/s-adenosyl-methionine-regulates-calcium-channels-and-inhibits-uterine-smooth-muscle-contraction-in-rats-with-infectious-premature-delivery-through-the-transient-receptor-protein-3-protein-kinase-c%C3%AE-c-kinase-activated-protein-phosphatase-1-inhibitor-of-17-kda
#1
Jing Ge, Tao Han, Xiaoqiu Li, Lili Shan, Jinhuan Zhang, Yan Hong, Yanqiu Xia, Jun Wang, Mingxiao Hou
The aim of the present study was to investigate the effects of S-adenosyl methionine (SAMe) on infectious premature inflammatory factors and uterine contraction, and to further explore its mechanism of action via the transient receptor protein 3 (TRPC3)/protein kinase Cβ (PKCβ)/C-kinase-activated protein phosphatase-1 inhibitor of 17 kDa (CPI-17) signaling pathway, following intervention by a TRPC3 inhibitor. A rat model of premature delivery induced by lipopolysaccharide (LPS) was established. Following treatment with SAMe and inhibiting TRPC3 expression, rat serum and uterus were isolated...
July 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29872396/trpc5-enos-axis-negatively-regulates-atp-induced-cardiomyocyte-hypertrophy
#2
Caroline Sunggip, Kakeru Shimoda, Sayaka Oda, Tomohiro Tanaka, Kazuhiro Nishiyama, Supachoke Mangmool, Akiyuki Nishimura, Takuro Numaga-Tomita, Motohiro Nishida
Cardiac hypertrophy, induced by neurohumoral factors, including angiotensin II and endothelin-1, is a major predisposing factor for heart failure. These ligands can induce hypertrophic growth of neonatal rat cardiomyocytes (NRCMs) mainly through Ca2+ -dependent calcineurin/nuclear factor of activated T cell (NFAT) signaling pathways activated by diacylglycerol-activated transient receptor potential canonical 3 and 6 (TRPC3/6) heteromultimer channels. Although extracellular nucleotide, adenosine 5'-triphosphate (ATP), is also known as most potent Ca2+ -mobilizing ligand that acts on purinergic receptors, ATP never induces cardiomyocyte hypertrophy...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29871977/a-multi-protein-complex-with-trpc-pde1c-and-a-2-r-plays-a-critical-role-in-regulating-cardiomyocyte-camp-and-survival
#3
Yishuai Zhang, Walter Knight, Si Chen, Amy Mohan, Chen Yan
Background -cAMP plays a critical role in regulating cardiomyocyte survival. Various cAMP signaling pathways behave distinctly or in opposition. We have previously reported that activation of cAMP hydrolysis by cyclic nucleotide phosphodiesterase 1C (PDE1C) promotes cardiomyocytes death/apoptosis, yet the underlying molecular mechanism remains unknown. In this study, we aimed to identify the specific cAMP signaling pathway modulated by PDE1C and determine the mechanism by which Ca2+ /calmodulin-stimulated PDE1C is activated...
June 5, 2018: Circulation
https://www.readbyqxmd.com/read/29859875/pyrazolo-1-5-a-pyrimidine-trpc6-antagonists-for-the-treatment-of-gastric-cancer
#4
Mingmin Ding, Hongbo Wang, Chunrong Qu, Fuchun Xu, Yingmin Zhu, Guangyao Lv, Yungang Lu, Qingjun Zhou, Hui Zhou, Xiaodong Zeng, Jingwen Zhang, Chunhong Yan, Jiacheng Lin, Huai-Rong Luo, Zixing Deng, Yuling Xiao, Jinbin Tian, Michael X Zhu, Xuechuan Hong
Transient receptor potential canonical 6 (TRPC6) proteins form receptor-operated Ca2+ -permeable channels, which have been thought to bring benefit to the treatment of diseases, including cancer. However, selective antagonists for TRPC channels are rare and none of them has been tested against gastric cancer. Compound 14a and analogs were synthesized by chemical elaboration of previously reported TRPC3/6/7 agonist 4o. 14a had very weak agonist activity at TRPC6 expressed in HEK293 cells but exhibited strong inhibition on both 4o-mediated and receptor-operated activation of TRPC6 with an IC50 of about 1 μM...
May 31, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29859013/tonantzitlolone-is-a-nanomolar-potency-activator-of-trpc1-4-5-channels
#5
Hussein N Rubaiy, Melanie J Ludlow, Karsten Siems, Katherine Norman, Richard Foster, Dietmar Wolf, John A Beutler, David J Beech
BACKGROUND AND PURPOSE: The diterpene ester tonantzitlonone (TZL) is a natural product which displays cytotoxicity towards certain types of cancer cell such as renal cell carcinoma cells. The effect is similar to that of (-)-Englerin A (EA) and so, although it is chemically distinct, we investigated whether TZL also targets transient receptor potential canonical (TRPC) channels of the TRPC1, TRPC4 and TRPC5 type (TRPC1/4/5 channels). EXPERIMENTAL APPROACH: Renal cell carcinoma A498 cells natively expressing TRPC1 and TRPC4, modified HEK 293 cells over expressing TRPC4, TRPC5, TRPC4-TRPC1 or TRPC5-TRPC1 concatemer, TRPC3 or TRPM2 or CHO cells over expressing TRPV4 were studied by intracellular Ca2+ measurement or whole-cell or excised membrane patch-clamp electrophysiology...
June 2, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29785489/trpc6-inactivation-confers-protection-in-a-model-of-severe-nephrosis-in-rats
#6
Eun Young Kim, Parisa Yazdizadeh Shotorbani, Stuart E Dryer
Mutations in canonical transient receptor potential-6 (TRPC6) channels give rise to rare familial forms of focal and segmental glomerulosclerosis (FSGS). Here we examined a possible role for TRPC6 in the progression of chronic puromycin aminonucleoside (PAN) nephrosis in Sprague-Dawley rats, a classic model of acquired nephrotic syndromes. We used CRISPR/Cas9 technology to delete a 239-bp region within exon 2 of the Trpc6 gene (Trpc6del allele). Trpc6del/del rats expressed detectable Trpc6 transcripts missing exon 2, and TRPC6 proteins could be detected by immunoblot of renal cortex...
May 22, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29752403/cryo-em-structure-of-the-cytoplasmic-domain-of-murine-transient-receptor-potential-cation-channel-subfamily-c-member-6-trpc6
#7
Caleigh M Azumaya, Francisco Sierra-Valdez, Julio F Cordero-Morales, Terunaga Nakagawa
The kidney maintains the internal milieu by regulating the retention and excretion of proteins, ions, and small molecules. The glomerular podocyte forms the slit diaphragm of the ultrafiltration filter, whose damage leads to progressive kidney failure and focal segmental glomerulosclerosis (FSGS). The canonical transient receptor potential 6 (TRPC6) ion channel is expressed in the podocyte and mutations in its cytoplasmic domain cause FSGS in humans. In vitro evaluation of disease-causing mutations in TRPC6 has revealed that these genetic alterations result in abnormal ion channel gating...
May 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29748835/canonical-transient-receptor-potential-channel-3-contributes-to-febrile-seizure-inducing-neuronal-cell-death-and-neuroinflammation
#8
Dan Sun, Hui Ma, Jiehui Ma, Jing Wang, Xiaolong Deng, Chunhui Hu, Xianbo Deng
Febrile seizure (FS) counts as the most common seizures symptom in children undergoing recurrent seizures, posing a high risk to developing subsequent temporal lobe epilepsy. Canonical transient receptor potential channel (TRPC) members are identified as the FS-related genes in hyperthermia prone rats. However, the role of TRPC3 in hyperthermia-induced FS rats remains unclear. In the present study, we investigated whether TRPC3 functionally contributes to the development of FSs. Elevated TRPC3 mRNA and protein levels was detected in hyperthermia-induced FS rats and rat hippocampal neuron cells...
May 10, 2018: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/29726814/structure-of-the-human-lipid-gated-cation-channel-trpc3
#9
Chen Fan, Wooyoung Choi, Weinan Sun, Juan Du, Wei Lu
The TRPC channels are crucially involved in store-operated calcium entry and calcium homeostasis, and they are implicated in human diseases such as neurodegenerative disease, cardiac hypertrophy, and spinocerebellar ataxia. We present a structure of the full-length human TRPC3, a lipid-gated TRPC member, in a lipid-occupied, closed state at 3.3 Angstrom. TRPC3 has four elbow-like membrane reentrant helices prior to the first transmembrane helix. The TRP helix is perpendicular to, and thus disengaged from, the pore-lining S6, suggesting a different gating mechanism from other TRP subfamily channels...
May 4, 2018: ELife
https://www.readbyqxmd.com/read/29700422/structure-of-the-receptor-activated-human-trpc6-and-trpc3-ion-channels
#10
Qinglin Tang, Wenjun Guo, Li Zheng, Jing-Xiang Wu, Meng Liu, Xindi Zhou, Xiaolin Zhang, Lei Chen
TRPC6 and TRPC3 are receptor-activated nonselective cation channels that belong to the family of canonical transient receptor potential (TRPC) channels. They are activated by diacylglycerol, a lipid second messenger. TRPC6 and TRPC3 are involved in many physiological processes and implicated in human genetic diseases. Here we present the structure of human TRPC6 homotetramer in complex with a newly identified high-affinity inhibitor BTDM solved by single-particle cryo-electron microscopy to 3.8 Å resolution...
April 26, 2018: Cell Research
https://www.readbyqxmd.com/read/29628897/stanniocalcin-2-regulates-non-capacitative-ca-2-entry-and-aggregation-in-mouse-platelets
#11
Esther López, L Gómez-Gordo, Carlos Cantonero, Nuria Bermejo, Jorge Pérez-Gómez, María P Granados, Gines M Salido, Juan A Rosado Dionisio, Pedro C Redondo Liberal
Stanniocalcin 2 (STC2) is a fish protein that controls body Ca2+ and phosphate metabolism. STC2 has also been described in mammals, and as platelet function highly depends on both extracellular and intracellular Ca2+ , we have explored its expression and function in these cells. STC2-/- mice exhibit shorter tail bleeding time than WT mice. Platelets from STC2-deficient mice showed enhanced aggregation, as well as enhanced Ca2+ mobilization in response to the physiological agonist thrombin (Thr) and the diacylglycerol analog, OAG, a selective activator of the non-capacitative Ca2+ entry channels...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29624776/trpc3-overexpression-and-intervention-in-airway-smooth-muscle-of-ovalbumin-induced-hyperresponsiveness-and-remodeling
#12
Bo-Ming Xu, Jia-Hua Zhang, Jia-Ling Wang, Jun-Hua Xiao
Transient receptor potential canonical channel 3 (TRPC3) proteins function as non-voltage-gated Ca2+ -permeable channels and play divergent roles in many processes of pathophysiology. The purpose of this study was to determine the relationship between TRPC3 expression and airway hyperresponsiveness and remodeling in ovalbumin-induced asthmatic Kunming mice. Mice were sensitized and challenged by ovalbumin to establish asthmatic model. Hematoxylin-eosin staining, hydroxyproline assay, and isometric tracheal ring force measurement were used to evaluate airway remodeling and hyperresponsiveness in asthmatic mice...
April 6, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29617457/sur1-trpm4-channel-activation-and-phasic-secretion-of-mmp-9-induced-by-tpa-in-brain-endothelial-cells
#13
Volodymyr Gerzanich, Min Seong Kwon, Seung Kyoon Woo, Alexander Ivanov, J Marc Simard
BACKGROUND: Hemorrhagic transformation is a major complication of ischemic stroke, is linked to matrix metalloproteinase-9 (MMP-9), and is exacerbated by tissue plasminogen activator (tPA). Cerebral ischemia/reperfusion is characterized by SUR1-TRPM4 (sulfonylurea receptor 1-transient receptor potential melastatin 4) channel upregulation in microvascular endothelium. In humans and rodents with cerebral ischemia/reperfusion (I/R), the SUR1 antagonist, glibenclamide, reduces hemorrhagic transformation and plasma MMP-9, but the mechanism is unknown...
2018: PloS One
https://www.readbyqxmd.com/read/29574924/the-effects-of-transient-receptor-potential-channel-trpc-on-airway-smooth-muscle-cell-isolated-from-asthma-model-mice
#14
Xiaoyu Zhang, Zhixin Zhao, Lijun Ma, Yali Guo, Xiaosu Li, Limin Zhao, Cuijie Tian, Xueyi Tang, Dongjun Cheng, Zhuochang Chen, Luoxian Zhang
This study aimed to validate whether transient receptor potential channel1 (TRPC1) and TRPC3 participate in the regulation the proliferation of airway smooth muscle cells (ASMCs) through modulating calcium ion (Ca2+ ) influx in vitro. Chronic model of murine asthma was induced and ASMCs isolated from asthmatic mice were used in this whole study. TRPC1 and TRPC3 were upregulated in asthmatic mouse ASMCs and selected for further investigation. Ca2+ concentration and the cell viability of asthmatic mouse ASMCs were significantly higher than that from non- asthma mice, however, TRPC channels blocker SKF96365 alleviated these effects...
March 25, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29561829/the-role-of-endothelial-ca-2-signaling-in-neurovascular-coupling-a-view-from-the-lumen
#15
REVIEW
Germano Guerra, Angela Lucariello, Angelica Perna, Laura Botta, Antonio De Luca, Francesco Moccia
BACKGROUND: Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity (NA) leads to local elevation in cerebral blood flow (CBF) to match the metabolic requirements of firing neurons. Following synaptic activity, an increase in neuronal and/or astrocyte Ca2+ concentration leads to the synthesis of multiple vasoactive messengers. Curiously, the role of endothelial Ca2+ signaling in NVC has been rather neglected, although endothelial cells are known to control the vascular tone in a Ca2+ -dependent manner throughout peripheral vasculature...
March 21, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29556099/an-optically-controlled-probe-identifies-lipid-gating-fenestrations-within-the-trpc3-channel
#16
Michaela Lichtenegger, Oleksandra Tiapko, Barbora Svobodova, Thomas Stockner, Toma N Glasnov, Wolfgang Schreibmayer, Dieter Platzer, Gema Guedes de la Cruz, Sarah Krenn, Romana Schober, Niroj Shrestha, Rainer Schindl, Christoph Romanin, Klaus Groschner
Transient receptor potential canonical (TRPC) channels TRPC3, TRPC6 and TRPC7 are able to sense the lipid messenger diacylglycerol (DAG). The DAG-sensing and lipid-gating processes in these ion channels are still unknown. To gain insights into the lipid-sensing principle, we generated a DAG photoswitch, OptoDArG, that enabled efficient control of TRPC3 by light. A structure-guided mutagenesis screen of the TRPC3 pore domain unveiled a single glycine residue behind the selectivity filter (G652) that is exposed to lipid through a subunit-joining fenestration...
April 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/29522264/a-larixol-congener-with-high-affinity-and-subtype-selectivity-toward-trpc6
#17
Stephanie Häfner, Finn Burg, Martina Kannler, Nicole Urban, Peter Mayer, Alexander Dietrich, Dirk Trauner, Johannes Broichhagen, Michael Schaefer
Natural products have many health benefits, and their application can improve the quality of life. Recently, the diterpene (+)-larixol and its acetylated congeners demonstrated selective inhibition of the second-messenger-gated cation channel transient receptor potential canonical 6 (TRPC6) over its close isoforms TRPC3 and TRPC7. Building on this knowledge, we expanded these findings by chemical diversification of (+)-larixol mostly at position C6. Implementing high-throughput Ca2+ FLIPR screening assays and electrophysiological patch-clamp recordings, we showcase larixyl N-methylcarbamate, termed SH045, as a compound with nanomolar affinity and 13-fold subtype selectivity over TRPC3 in stably expressing HEK293 cells...
March 9, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29449621/polygonum-aviculare-l-extract-and-quercetin-attenuate-contraction-in-airway-smooth-muscle
#18
Xi Luo, Lu Xue, Hao Xu, Qing-Yang Zhao, Qian Wang, Yu-Shan She, Dun-An Zang, Jinhua Shen, Yong-Bo Peng, Ping Zhao, Meng-Fei Yu, Weiwei Chen, Li-Qun Ma, Shu Chen, Shanshan Chen, Xiangning Fu, Sheng Hu, Xiaowei Nie, Chenyou Shen, Chunbin Zou, Gangjian Qin, Jiapei Dai, Guangju Ji, Yunchao Su, Shen Hu, Jingyu Chen, Qing-Hua Liu
Because of the serious side effects of the currently used bronchodilators, new compounds with similar functions must be developed. We screened several herbs and found that Polygonum aviculare L. contains ingredients that inhibit the precontraction of mouse and human airway smooth muscle (ASM). High K+ -induced precontraction in ASM was completely inhibited by nifedipine, a selective blocker of L-type voltage-dependent Ca2+ channels (LVDCCs). However, nifedipine only partially reduced the precontraction induced by acetylcholine chloride (ACH)...
February 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29438802/endocannabinoid-signaling-in-embryonic-neuronal-motility-and-cell-cell-contact-role-of-mglur5-and-trpc3-channels
#19
Pauli M Turunen, Lauri M Louhivuori, Verna Louhivuori, Jyrki P Kukkonen, Karl E Åkerman
Cell-cell communication plays a central role in the guidance of migrating neuronal precursor cells during the development of the cerebral cortex. Endocannabinoids (eCBs) have previously been shown to be one of the central factors regulating neuronal migration. In this study the effects of eCBs on different parameters, expected to affect embryonic cortical neuronal motility have been analyzed in neurosphere-derived neuroblasts using time-lapse microscopy. Increased endogenous production of the endocannabinoid 2-arachidonyl glycerol (2-AG) causes bursts of neuroblast motility...
April 1, 2018: Neuroscience
https://www.readbyqxmd.com/read/29436640/-corrigendum-roles-and-mechanisms-of-trpc3-and-the-plc%C3%AE-pkc-cpi-17-signaling-pathway-in-regulating-parturition
#20
Jing Chen, Dongming Zheng, Hong Cui, Sishi Liu, Lijuan Zhang, Caixia Liu
Subsequent to the publication of the above paper, the authors have realized that there were errors in Fig. 1 on page 902; essentially, the experimental data described as being 'Preterm' and 'Infected preterm' should have been labelled as 'Full‑term without labor' and 'Preterm', respectively. Note that these errors in Fig. 1 were not reflected in the published figure legend. The corrected version of Fig. 1 is shown here. The authors sincerely apologize for this mistake, and regret any inconvenience this mistake has caused...
April 2018: Molecular Medicine Reports
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