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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
#1
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/29693628/influence-of-mechanical-unloading-on-articular-chondrocyte-dedifferentiation
#2
Simon L Wuest, Martina Caliò, Timon Wernas, Samuel Tanner, Christina Giger-Lange, Fabienne Wyss, Fabian Ille, Benjamin Gantenbein, Marcel Egli
Due to the limited self-repair capacity of articular cartilage, the surgical restoration of defective cartilage remains a major clinical challenge. The cell-based approach, which is known as autologous chondrocyte transplantation (ACT), has limited success, presumably because the chondrocytes acquire a fibroblast-like phenotype in monolayer culture. This unwanted dedifferentiation process is typically addressed by using three-dimensional scaffolds, pellet culture, and/or the application of exogenous factors...
April 25, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29660945/trpc1-null-exacerbates-memory-deficit-and-apoptosis-induced-by-amyloid-%C3%AE
#3
Mengzhu Li, Enjie Liu, Qiuzhi Zhou, Shihong Li, Xin Wang, Yanchao Liu, Lin Wang, Dongsheng Sun, Jinwang Ye, Yuan Gao, Xifei Yang, Jianjun Liu, Ying Yang, Jian-Zhi Wang
The transient receptor potential cation (TRPC) channels are widely expressed in nervous system but their functions remain largely unclear. Here, we found that TRPC1 deletion did not affect learning and memory in physiological conditions, while it aggravated learning and memory deficits induced by amyloid-β (Aβ), the major component of the senile plaques observed in the brains of Alzheimer's disease (AD). Further studies demonstrated that TRPC1 deletion did not affect cell apoptosis in physiological condition, but it exacerbated the Aβ-induced cell death in mouse hippocampus...
April 11, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29615894/trpc1-deletion-causes-striatal-neuronal-cell-apoptosis-and-proteomic-alterations-in-mice
#4
Dian Wang, Haitao Yu, Benhong Xu, Hua Xu, Zaijun Zhang, Xiaohu Ren, Jianhui Yuan, Jianjun Liu, Yi Guo, Peter S Spencer, Xifei Yang
Transient receptor potential channel 1 (TRPC1) is widely expressed throughout the nervous system, while its biological role remains unclear. In this study, we showed that TRPC1 deletion caused striatal neuronal loss and significantly increased TUNEL-positive and 8-hydroxy-2'-deoxyguanosine (8-OHdG) staining in the striatum. Proteomic analysis by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS) revealed a total of 51 differentially expressed proteins (26 increased and 25 decreased) in the stratum of TRPC1 knockout (TRPC1-/- ) mice compared to that of wild type (WT) mice...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29581825/novel-inhibitor-candidates-of-trpv2-prevent-damage-of-dystrophic-myocytes-and-ameliorate-against-dilated-cardiomyopathy-in-a-hamster-model
#5
Yuko Iwata, Yoshimi Katayama, Yasushi Okuno, Shigeo Wakabayashi
Transient receptor potential cation channel, subfamily V, member 2 (TRPV2) is a principal candidate for abnormal Ca2+ -entry pathways, which is a potential target for therapy of muscular dystrophy and cardiomyopathy. Here, an in silico drug screening and the following cell-based screening to measure the TRPV2 activation were carried out in HEK293 cells expressing TRPV2 using lead compounds (tranilast or SKF96365) and off-patent drug stocks. We identified 4 chemical compounds containing amino-benzoyl groups and 1 compound (lumin) containing an ethylquinolinium group as candidate TRPV2 inhibitors...
March 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29574924/the-effects-of-transient-receptor-potential-channel-trpc-on-airway-smooth-muscle-cell-isolated-from-asthma-model-mice
#6
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/29570903/trpc1-3-6-inhibition-attenuates-the-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-in-gastric-cancer-via-the-ras-raf1-erk-signaling-pathway
#7
Pengbo Ge, Linting Wei, Mingkai Zhang, Baoguang Hu, Kai Wang, Yanbin Li, Shuaichen Liu, Jianping Wang, Yuming Li
Gastric cancer (GC) is one of the most common malignancies worldwide. TGF-β1 induces the epithelial-mesenchymal transition (EMT) in GC, mainly through Smad-dependent pathways. Nevertheless, few studies have focused on the activation of non-canonical transduction pathways. TRPC, Ca2+ entry channels, are ubiquitously expressed in various cell types and are involved in many cellular functions. However, their roles in GC are not well elucidated. This study aimed to determine whether TRPC participates in the TGF-β1-induced EMT of GC and to investigate the potential mechanisms...
March 23, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29560783/trpc6-and-trpc4-heteromultimerization-mediates-store-depletion-activated-ncx1-reversal-in-proliferative-vascular-smooth-muscle-cells
#8
Bin Zhang, Bei Liu, Carolyn M Roos, Michael A Thompson, Y S Prakash, Jordan D Miller, Rui-Wei Guo
Store depletion has been shown to induce Ca2+ entry by Na+/Ca+ exchange (NCX) 1 reversal in proliferative vascular smooth muscle cells (VSMCs). The study objective was to investigate the role of transient receptor potential canonical (TRPC) channels in store depletion and NCX1 reversal in proliferative VSMCs. In cultured VSMCs, expressing TRPC1, TRPC4, and TRPC6, the removal of extracellular Na+ was followed by a significant increase of cytosolic Ca2+ concentration that was inhibited by KBR, a selective NCX1 inhibitor...
March 21, 2018: Channels
https://www.readbyqxmd.com/read/29549288/shenfu-injection-attenuates-rat-myocardial-hypertrophy-by-up-regulating-mir-19a-3p-expression
#9
Zhu-Jun Mao, Quan-Long Zhang, Jia Shang, Ting Gao, Wen-Jun Yuan, Lu-Ping Qin
Shenfu Injection (SFI) is a classical Chinese medicine used to treat heart failure. Our previous study demonstrated that miRNAs underwent changes in rats with myocardial hypertrophy induced by abdominal aortic constriction. Interestingly, there was a significant change in miR-19a-3p, whose target gene is known to be associated with MEF2 signaling. However, whether and how SFI regulates miR-19a-3p in the treatment of myocardial hypertrophy has not been investigated. The purpose of the present study was to investigate the regulatory effect of SFI on miR-19a-3p in MEF2 signaling in the rat hypertrophic myocardium...
March 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29535613/trpc1-channels-are-expressed-in-pyramidal-neurons-and-in-a-subset-of-somatostatin-interneurons-in-the-rat-neocortex
#10
Juan R Martinez-Galan, Ana Verdejo, Elena Caminos
Disturbances in calcium homeostasis due to canonical transient receptor potential (TRPC) and/or store-operated calcium (SOC) channels can play a key role in a large number of brain disorders. TRPC channels are plasma membrane cation channels included in the transient receptor potential (TRP) superfamily. The most widely distributed member of the TRPC subfamily in the brain is TRPC1, which is frequently linked to group I metabotropic glutamate receptors (mGluRs) and to the components of SOC channels. Proposing TRPC/SOC channels as a therapeutic target in neurological diseases previously requires a detailed knowledge of the distribution of such molecules in the brain...
2018: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/29532428/trpc1-deficiency-impairs-the-endothelial-progenitor-cell-function-via-inhibition-of-calmodulin-enos-pathway
#11
Lai-Ling Du, Zhida Shen, Zhengwei Li, Xuewei Ye, Meiping Wu, Lihui Hong, Yanbo Zhao
Endothelial progenitor cells (EPCs) promote angiogenesis and play a pivotal role in endothelial repair and re-endothelialization after vascular injury. Transient receptor potential-canonical1 (TRPC1) has been recently implied to play important roles on EPC function. Here, we studied the role of TRPC1 in regulating EPC function in vivo and in vitro. EPCs were cultured from TRPC1-knockout mice and their controls. In vitro, TRPC1 knockout reduced EPC functional activities, including migration and tube formation...
March 12, 2018: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/29531834/bcl-2-regulates-store-operated-ca-2-entry-to-modulate-er-stress-induced-apoptosis
#12
Wen-Tai Chiu, Heng-Ai Chang, Yi-Hsin Lin, Yu-Shan Lin, Hsiao-Tzu Chang, Hsi-Hui Lin, Soon-Cen Huang, Ming-Jer Tang, Meng-Ru Shen
Ca2+ plays a significant role in linking the induction of apoptosis. The key anti-apoptotic protein, Bcl-2, has been reported to regulate the movement of Ca2+ across the ER membrane, but the exact effect of Bcl-2 on Ca2+ levels remains controversial. Store-operated Ca2+ entry (SOCE), a major mode of Ca2+ uptake in non-excitable cells, is activated by depletion of Ca2+ in the ER. Depletion of Ca2+ in the ER causes translocation of the SOC channel activator, STIM1, to the plasma membrane. Thereafter, STIM1 binds to Orai1 or/and TRPC1 channels, forcing them to open and thereby allow Ca2+ entry...
December 2018: Cell Death Discovery
https://www.readbyqxmd.com/read/29524421/a-mechanically-activated-trpc1-like-current-in-white-adipocytes
#13
Mickaël F El Hachmane, Charlotta S Olofsson
Ca2+ impacts a large array of cellular processes in every known cell type. In the white adipocyte, Ca2+ is involved in regulation of metabolic processes such as lipolysis, glucose uptake and hormone secretion. Although the importance of Ca2+ in control of white adipocyte function is clear, knowledge is still lacking regarding the control of dynamic Ca2+ alterations within adipocytes and mechanisms inducing intracellular Ca2+ changes remain elusive. Own work has recently demonstrated the existence of store-operated Ca2+ entry (SOCE) in lipid filled adipocytes...
April 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29480205/inhibition-of-trpc1-dependent-store-operated-calcium-entry-improves-synaptic-stability-and-motor-performance-in-a-mouse-model-of-huntington-s-disease
#14
Jun Wu, Daniel Ryskamp, Lutz Birnbaumer, Ilya Bezprozvanny
BACKGROUND: Huntington disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. We previously discovered that mutant Huntingtin sensitizes type 1 inositol 1,4,5-trisphosphate receptor (InsP3R1) to InsP3. This causes calcium leakage from the endoplasmic reticulum (ER) and a compensatory increase in neuronal store-operated calcium (nSOC) entry. We previously demonstrated that supranormal nSOC leads to synaptic loss in striatal medium spiny neurons (MSNs) in YAC128 HD mice...
2018: Journal of Huntington's Disease
https://www.readbyqxmd.com/read/29445096/chronic-intermittent-hypoxia-promotes-myocardial-ischemia-related-ventricular-arrhythmias-and-sudden-cardiac-death
#15
Jessica Morand, Claire Arnaud, Jean-Louis Pepin, Diane Godin-Ribuot
We investigated the effects of intermittent hypoxia (IH), such as that encountered in severe obstructive sleep apnea (OSA) patients, on the development and severity of myocardial ischemia-related ventricular arrhythmias. Rats were exposed to 14 days of IH (30 s at 5%O2 and 30 s at 21%O2 , 8 h·day-1 ) or normoxia (N, similar air-air cycles) and submitted to a 30-min coronary ligature. Arterial blood pressure (BP) and ECG were recorded for power spectral analysis, ECG interval measurement and arrhythmia quantification...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29438745/an-automated-epifluorescence-microscopy-imaging-assay-for-the-identification-of-phospho-akt-level-modulators-in-breast-cancer-cells
#16
Elke Kaemmerer, Dane Turner, Amelia A Peters, Sarah J Roberts-Thomson, Gregory R Monteith
AKT is an enzyme of the PI3K/pAKT pathway, regulating proliferation and cell survival. High basal levels of active, phosphorylated AKT (pAKT) are associated with tumor progression and therapeutic resistance in some breast cancer subtypes, including HER2 positive breast cancers. Various stimuli can increase pAKT levels and elevated basal pAKT levels are a feature of PTEN-deficient breast cancer cell lines. The aim of this study was to develop an assay able to identify modulators of pAKT levels using an automated epifluorescence microscope and high content analysis...
February 10, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/29385160/treatment-with-hc-070-a-potent-inhibitor-of-trpc4-and-trpc5-leads-to-anxiolytic-and-antidepressant-effects-in-mice
#17
Stefan Just, Bertrand L Chenard, Angelo Ceci, Timothy Strassmaier, Jayhong A Chong, Nathaniel T Blair, Randall J Gallaschun, Donato Del Camino, Susan Cantin, Marc D'Amours, Christian Eickmeier, Christopher M Fanger, Carsten Hecker, David P Hessler, Bastian Hengerer, Katja S Kroker, Sam Malekiani, Robert Mihalek, Joseph McLaughlin, Georg Rast, JoAnn Witek, Achim Sauer, Christopher R Pryce, Magdalene M Moran
BACKGROUND: Forty million adults in the US suffer from anxiety disorders, making these the most common forms of mental illness. Transient receptor potential channel canonical subfamily (TRPC) members 4 and 5 are non-selective cation channels highly expressed in regions of the cortex and amygdala, areas thought to be important in regulating anxiety. Previous work with null mice suggests that inhibition of TRPC4 and TRPC5 may have anxiolytic effects. HC-070 IN VITRO: To assess the potential of TRPC4/5 inhibitors as an avenue for treatment, we invented a highly potent, small molecule antagonist of TRPC4 and TRPC5 which we call HC-070...
2018: PloS One
https://www.readbyqxmd.com/read/29373286/trpc-proteins-contribute-to-development-of-diabetic-retinopathy-and-regulate-glyoxalase-1-activity-and-methylglyoxal-accumulation
#18
Robin Sachdeva, Andrea Schlotterer, Dagmar Schumacher, Christin Matka, Ilka Mathar, Nadine Dietrich, Rebekka Medert, Ulrich Kriebs, Jihong Lin, Peter Nawroth, Lutz Birnbaumer, Thomas Fleming, Hans-Peter Hammes, Marc Freichel
OBJECTIVE: Diabetic retinopathy (DR) is induced by an accumulation of reactive metabolites such as ROS, RNS, and RCS species, which were reported to modulate the activity of cation channels of the TRPC family. In this study, we use Trpc1/4/5/6-/- compound knockout mice to analyze the contribution of these TRPC proteins to diabetic retinopathy. METHODS: We used Nanostring- and qPCR-based analysis to determine mRNA levels of TRPC channels in control and diabetic retinae and retinal cell types...
March 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29359518/store-operated-calcium-entries-control-neural-stem-cell-self-renewal-in-the-adult-brain-subventricular-zone
#19
Florence Domenichini, Elodie Terrié, Patricia Arnault, Thomas Harnois, Christophe Magaud, Patrick Bois, Bruno Constantin, Valérie Coronas
The subventricular zone (SVZ) is the major stem cell niche in the brain of adult mammals. Within this region, neural stem cells (NSC) proliferate, self-renew and give birth to neurons and glial cells. Previous studies underlined enrichment in calcium signaling-related transcripts in adult NSC. Because of their ability to mobilize sustained calcium influxes in response to a wide range of extracellular factors, store-operated channels (SOC) appear to be, among calcium channels, relevant candidates to induce calcium signaling in NSC whose cellular activities are continuously adapted to physiological signals from the microenvironment...
January 23, 2018: Stem Cells
https://www.readbyqxmd.com/read/29324706/endothelial-ca-2-signaling-and-the-resistance-to-anticancer-treatments-partners-in-crime
#20
REVIEW
Francesco Moccia
Intracellular Ca2+ signaling drives angiogenesis and vasculogenesis by stimulating proliferation, migration, and tube formation in both vascular endothelial cells and endothelial colony forming cells (ECFCs), which represent the only endothelial precursor truly belonging to the endothelial phenotype. In addition, local Ca2+ signals at the endoplasmic reticulum (ER)-mitochondria interface regulate endothelial cell fate by stimulating survival or apoptosis depending on the extent of the mitochondrial Ca2+ increase...
January 11, 2018: International Journal of Molecular Sciences
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