Read by QxMD icon Read


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
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
Petra Eder
TRPC channels have been suggested as potential candidates mediating store-operated Ca2+ 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
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
Nicole Urban, Sonja Neuser, Anika Hentschel, Sebastian Köhling, Jörg Rademann, Michael Schaefer
BACKGROUND AND PURPOSE: Gain of function mutations in TRPC6 channels can cause autosomal dominant forms of focal segmental glomerulosclerosis (FSGS). Validated inhibitors of TRPC6 channels that are biologically active on FSGS-related TRPC6 mutants are eagerly sought. EXPERIMENTAL APPROACH: We synthesized new TRPC6-inhibiting modulators from larixol, a resiniferous constituent of Larix decidua, and tested the potency and selectivity in cell lines stably expressing various TRPC channel isoforms...
November 2017: British Journal of Pharmacology
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
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
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
Zili Zhang, Jian Wang, Jianxing He, Xiansheng Zeng, Xindong Chen, Mingmei Xiong, Qipeng Zhou, Meihua Guo, Defu Li, Wenju Lu
OBJECTIVE: Store operated calcium channels (SOCCs) and Receptor-operated calcium channels (ROCCs) are important pathways participating in regulation of intracellular Ca(2 +) concentration in various cell types. The purpose of our study is to determine whether genetic variations in key components of SOCCs and ROCCs are associated with lung cancer risk. METHODS: We identified 236 tagSNPs in 9 key genes related to SOCCs and ROCCs (TRPC1, TRPC3, TRPC4, TRPC6, TRPC7, ORAI1, ORAI2, STIM1, and STIM2) and evaluated their association with lung cancer risk in a two-stage case-control study with a total of 2433 lung cancer cases and 2433 cancer-free controls using Illumina high throughput genotyping platform...
September 2016: Meta Gene
Szilvia Fiatal, Réka Tóth, Ágota Moravcsik-Kornyicki, Zsigmond Kósa, János Sándor, Martin McKee, Róza Ádány
INTRODUCTION: The prevalence of smoking in Romani of both genders is significantly higher than in the general population. Our aim was to determine whether a genetic susceptibility contributes to the high prevalence of smoking among Roma in a study based on data collected from cross-sectional surveys. METHODS: Twenty single nucleotide polymorphisms known to be closely related to smoking behavior were investigated in DNA samples of Hungarian Roma (N = 1273) and general (N = 2388) populations...
December 2016: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
(no author information available yet)
No abstract text is available yet for this article.
2016: Journal of Cardiovascular Pharmacology
Xuexin Zhang, Amy M Spinelli, Timothy Masiello, Mohamed Trebak
Transient receptor potential canonical subfamily, member 7 (TRPC7) is the most recently identified member of the TRPC family of Ca(2+)-permeable non-selective cation channels. The gene encoding the TRPC7 channel plasma membrane protein was first cloned from mouse brain. TRPC7 mRNA and protein have been detected in cell types derived from multiple organ systems from various species including humans. Gq-coupled protein receptor activation is the predominant mode of TRPC7 activation. Lipid metabolites involved in the phospholipase C (PLC) signaling pathway, including diacylglycerol (DAG) and its precursor the phosphatidylinositol-4,5-bisphosphate (PIP2), have been shown to be direct regulators of TRPC7 channel...
2016: Advances in Experimental Medicine and Biology
Seishiro Sawamura, Masahiko Hatano, Yoshinori Takada, Kyosuke Hino, Tetsuya Kawamura, Jun Tanikawa, Hiroshi Nakagawa, Hideharu Hase, Akito Nakao, Mitsuru Hirano, Rachapun Rotrattanadumrong, Shigeki Kiyonaka, Masayuki X Mori, Motohiro Nishida, Yaopeng Hu, Ryuji Inoue, Ryu Nagata, Yasuo Mori
Transient receptor potential canonical (TRPC) proteins form Ca(2+)-permeable cation channels activated upon stimulation of metabotropic receptors coupled to phospholipase C. Among the TRPC subfamily, TRPC3 and TRPC6 channels activated directly by diacylglycerol (DAG) play important roles in brain-derived neurotrophic factor (BDNF) signaling, promoting neuronal development and survival. In various disease models, BDNF restores neurologic deficits, but its therapeutic potential is limited by its poor pharmacokinetic profile...
March 2016: Molecular Pharmacology
Nicole Urban, Liming Wang, Sandra Kwiek, Jörg Rademann, Wolfgang M Kuebler, Michael Schaefer
Classical or canonical transient receptor potential 6 (TRPC6), a nonselective and Ca(2+)-permeable cation channel, mediates pathophysiological responses within pulmonary and renal diseases that are still poorly controlled by current medication. Thus, controlling TRPC6 activity may provide a promising and challenging pharmacological approach. Recently identified chemical entities have demonstrated that TRPC6 is pharmacologically targetable. However, isotype-selectivity with regard to its closest relative, TRPC3, is difficult to achieve...
January 2016: Molecular Pharmacology
Sandeep Gopal, Pernille Søgaard, Hinke A B Multhaupt, Csilla Pataki, Elena Okina, Xiaojie Xian, Mikael E Pedersen, Troy Stevens, Oliver Griesbeck, Pyong Woo Park, Roger Pocock, John R Couchman
Transmembrane heparan sulfate proteoglycans regulate multiple aspects of cell behavior, but the molecular basis of their signaling is unresolved. The major family of transmembrane proteoglycans is the syndecans, present in virtually all nucleated cells, but with mostly unknown functions. Here, we show that syndecans regulate transient receptor potential canonical (TRPCs) channels to control cytosolic calcium equilibria and consequent cell behavior. In fibroblasts, ligand interactions with heparan sulfate of syndecan-4 recruit cytoplasmic protein kinase C to target serine714 of TRPC7 with subsequent control of the cytoskeleton and the myofibroblast phenotype...
September 28, 2015: Journal of Cell Biology
Long-Biao Cui, Bo-Wei Li, Chen Liang, Zheng Dong, Peng Chen, Chun-Rong Zhao, Yun-Chao Liu, Long-Long Zheng, Si-Bo Chen, Jie Xu, Xiao-Hang Jin, Juan Shi
OBJECTIVE: We aimed to investigate the expression characteristics of transient receptor potential canonical 7 (TRPC7) in normal and hypertrophic cardiac myocytes. METHODS: The 2-kidney 1-clip (2K1C) method was used to induce renovascular hypertension. Losartan, the potent inhibitor of angiotensin II (Ang II) receptor, was applied to the drinking water of 2K1C rats to inhibit Ang II-mediated responses. TRPC7 expression was examined by immunohisto/cytochemistry and Western blot analyses in normal and hypertrophic hearts...
February 2016: Journal of Cardiovascular Pharmacology
Xuan Qin, Ye Liu, Minghui Zhu, Zhuo Yang
Transient receptor potential canonical channel (TRPC) is a nonselective cation channel dominantly permeable to Ca(2+). It consists of seven homologues, TRPC1-TRPC7, based on their sequence similarity. According to some researches, the expression of TRPC3/5 in hippocampus is related to the morphological changes of hippocampus, including axon length and dendritic spine density [1]. This study observed whether the expression of TRPC3/5 was changed in chronic unpredictable stress (CUS)-induced depression of rat model and can the altered TRPC3/5 expression affect the morphology of neurons in hippocampus of depressive rats as well as the cognitive ability...
September 1, 2015: Behavioural Brain Research
T Maier, M Follmann, G Hessler, H-W Kleemann, S Hachtel, B Fuchs, N Weissmann, W Linz, T Schmidt, M Löhn, K Schroeter, L Wang, H Rütten, C Strübing
BACKGROUND AND PURPOSE: The cation channel transient receptor potential canonical (TRPC) 6 has been associated with several pathologies including focal segmental glomerulosclerosis, pulmonary hypertension and ischaemia reperfusion-induced lung oedema. We set out to discover novel inhibitors of TRPC6 channels and investigate the therapeutic potential of these agents. EXPERIMENTAL APPROACH: A library of potential TRPC channel inhibitors was designed and synthesized...
July 2015: British Journal of Pharmacology
Xiao-Hong Lin, Hua-Shan Hong, Guang-Rong Zou, Liang-Long Chen
BACKGROUND: Hypertension and its complications are associated with arterial remodeling. Transient receptor potential cationic channels (TRPCs) are important nonselective cationic channels that regulate calcium homeostasis in mammalian cell membranes. We aimed to study the expression of various TRPC isoforms in spontaneously hypertensive rat (SHR) carotid arterial remodeling and explore the relationship between SHR carotid arterial remodeling and TRPC expression. MATERIALS AND METHODS: Thirty male SHRs were randomly divided into three groups and sacrificed at ages 4, 8, and 18 wk, respectively, with matching control male Wistar-Kyoto rats (n = 10)...
May 1, 2015: Journal of Surgical Research
Letizia Albarrán, Natalia Dionisio, Esther Lopez, Ginés M Salido, Pedro C Redondo, Juan A Rosado
STIM1 (stromal interaction molecule 1) regulates store-operated channels in the plasma membrane, but the regulation of TRPC (transient receptor potential canonical) heteromultimerization and location by STIM1 is poorly understood. STIM1 is a single transmembrane protein that communicates the filling state of the endoplasmic reticulum to store-operated channels. STIM1 has been reported to regulate the activity of all of the TRPC family members, except TRPC7. TRPC6 has been predominantly associated to second messenger-activated Ca2+ entry pathways...
November 1, 2014: Biochemical Journal
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"