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"Calcium sensing receptor"

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https://www.readbyqxmd.com/read/29452090/activation-of-calcium-sensing-receptor-mediated-autophagy-in-angiotensinii-induced-cardiac-fibrosis-in-vitro
#1
Jinyu Chi, Lei Wang, Xiaohui Zhang, Yu Fu, Yue Liu, Wenjia Chen, Wenxiu Liu, Zhiyu Shi, Xinhua Yin
Cardiac fibrosis is one of the primary mechanisms of ventricular remodeling, and there is no effective method for reversal. Activation of calcium sensing receptor (CaSR) has been reported to be involved in the development of myocardial fibrosis, but the molecular mechanism for CaSR activation has not yet been clarified and needs to be further explored. Here, we found that AngII induces cardiac fibroblast proliferation and phenotypic transformation in a dose-dependent manner with increased CaSR and autophagy related protein (Beclin1, LC3B) expression...
February 13, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29449563/cinacalcet-mediated-activation-of-the-camkk%C3%AE-lkb1-ampk-pathway-attenuates-diabetic-nephropathy-in-db-db-mice-by-modulation-of-apoptosis-and-autophagy
#2
Ji Hee Lim, Hyung Wook Kim, Min Young Kim, Tae Woo Kim, Eun Nim Kim, Yaeni Kim, Sungjin Chung, Young Soo Kim, Bum Soon Choi, Yong-Soo Kim, Yoon Sik Chang, Hye Won Kim, Cheol Whee Park
Apoptosis and autophagy are harmoniously regulated biological processes for maintaining tissue homeostasis. AMP-activated protein kinase (AMPK) functions as a metabolic sensor to coordinate cellular survival and function in various organs, including the kidney. We investigated the renoprotective effects of cinacalcet in high-glucose treated human glomerular endothelial cells (HGECs), murine podocytes and C57BLKS/J-db/db mice. In cultured HGECs and podocytes, cinacalcet decreased oxidative stress and apoptosis and increased autophagy that were attributed to the increment of intracellular Ca2+ concentration and the phosphorylation of Ca2+ /calmodulin-dependent protein kinase kinaseβ (CaMKKβ)-Liver kinase B1 (LKB1)-AMPK and their downstream signals including the phosphorylation of endothelial nitric oxide synthase (eNOS) and increases in superoxide dismutases and B cell leukemia/lymphoma 2/BCL-2-associated X protein expression...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29445089/mir-27a-5p-increases-steer-fat-deposition-partly-by-targeting-calcium-sensing-receptor-casr
#3
Wucai Yang, Keqiong Tang, Yaning Wang, Linsen Zan
Castration increases fat deposition, improving beef quality in cattle. Here, the steer group exhibited a significantly higher intramuscular fat (IMF) content than the bull group. To determine the potential roles of microRNAs (miRNAs) in castration-induced fat deposition, differential expression patterns of miRNA in liver tissue were investigated in bulls and steers. A total of 7,827,294 clean reads were obtained from the bull liver library, and 8,312,483 were obtained from the steer liver library; 452 conserved bovine miRNAs and 20 novel miRNAs were identified...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29423207/old-and-new-calcimimetics-for-treatment-of-secondary-hyperparathyroidism-impact-on-biochemical-and-relevant-clinical-outcomes
#4
Luciano Pereira, Catarina Meng, Daniela Marques, João M Frazão
Secondary hyperparathyroidism (SHPT) is associated with increased bone turnover, risk of fractures, vascular calcifications, and cardiovascular and all-cause mortality. The classical treatment for SHPT includes active vitamin D compounds and phosphate binders. However, achieving the optimal laboratory targets is often difficult because vitamin D sterols suppress parathyroid hormone (PTH) secretion, while also promoting calcium and phosphate intestinal absorption. Calcimimetics increase the sensitivity of the calcium-sensing receptor, so that even with lower levels of extracellular calcium a signal can still exist, leading to a decrease of the set-point for systemic calcium homeostasis...
February 2018: Clinical Kidney Journal
https://www.readbyqxmd.com/read/29420171/ap2-mutations-impair-calcium-sensing-receptor-trafficking-and-signaling-and-show-an-endosomal-pathway-to-spatially-direct-g-protein-selectivity
#5
Caroline M Gorvin, Angela Rogers, Benoit Hastoy, Andrei I Tarasov, Morten Frost, Silvia Sposini, Asuka Inoue, Michael P Whyte, Patrik Rorsman, Aylin C Hanyaloglu, Gerda E Breitwieser, Rajesh V Thakker
Spatial control of G-protein-coupled receptor (GPCR) signaling, which is used by cells to translate complex information into distinct downstream responses, is achieved by using plasma membrane (PM) and endocytic-derived signaling pathways. The roles of the endomembrane in regulating such pleiotropic signaling via multiple G-protein pathways remain unknown. Here, we investigated the effects of disease-causing mutations of the adaptor protein-2 ? subunit (AP2?) on signaling by the class C GPCR calcium-sensing receptor (CaSR)...
January 23, 2018: Cell Reports
https://www.readbyqxmd.com/read/29397395/the-expression-of-calcium-sensing-receptor-in-normal-and-diabetic-rat-eyes
#6
Ping Jiang, Rong Huang, Nan Ma, Fagang Jiang
BACKGROUND Calcium sensing receptor (CaSR) is widely expressed in many tissues of the body, but it is rarely reported to be expressed in the eyes. This research explored the expression and distribution of CaSR in eye tissues of normal and diabetic rats. MATERIAL AND METHODS Thirty male Sprague Dawley (SD) rats were randomly divided into a diabetic and a normal group. Diabetes mellitus (DM) models were successfully established by intraperitoneal injection of streptozotocin. The expression and distribution of CaSR in the rat eyeballs were detected by immunohistochemistry...
February 4, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29387985/genetic-polymorphism-of-calcium-sensing-receptor-in-women-with-breast-cancer
#7
Larysse Maira Campos-Verdes, João Paulo da Silva-Sampaio, Danylo Rafhael Costa-Silva, Victor Alves de Oliveira, Airton Mendes Conde Junior, Vladimir Costa Silva, Airlane Pereira Alencar, Viriato Campelo, Pedro Vitor Lopes-Costa, Luiz Henrique Gebrim, Benedito Borges da Silva
Breast cancer is a disease of unknown etiology, whose major risk factors are genetic alterations. Polymorphism of the calcium-sensing receptor (CaSR) has been a focus of some recent studies, due to a probable association with breast cancer risk and tumor aggressiveness. A relationship between polymorphic rs17251221 variant of the CaSR gene, and allele G (considered a gain-of-function mutation) and breast cancer risk has been stressed, despite the paucity of studies found in the literature. The present study involved 137 women (69 women with breast cancer-case; and 68 controls without breast cancer) who had 3 ml of peripheral blood drawn for DNA study...
January 31, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29383416/calcium-receptor-signaling-and-citrate-transport
#8
Ryan W Walker, Shijia Zhang, Joycelynn A Coleman-Barnett, L Lee Hamm, Kathleen S Hering-Smith
The calcium sensing receptor (CaSR) in the distal nephron decreases the propensity for calcium stones. Here we investigate if the apical CaSR in the proximal tubule also prevents stone formation acting via regulation of apical dicarboxylate and citrate transport. Urinary citrate, partially reabsorbed as a dicarboxylate in the proximal tubule lumen, inhibits stone formation by complexing calcium. We previously demonstrated a novel apical calcium-sensitive dicarboxylate transport system in OK proximal tubule cells...
January 30, 2018: Urolithiasis
https://www.readbyqxmd.com/read/29379093/mcpip1-induced-autophagy-mediates-ischemia-reperfusion-injury-in-endothelial-cells-via-hmgb1-and-casr
#9
Xiaolong Xie, Tiebing Zhu, Lulu Chen, Shuang Ding, Han Chu, Jing Wang, Honghong Yao, Jie Chao
Monocyte chemotactic protein-1-induced protein 1 (MCPIP1) plays a important role in ischemia/reperfusion (I/R) injury. Autophagy is involved in activating endothelial cells in response to I/R. However, researchers have not clearly determined whether MCPIP1 mediates I/R injury in endothelial cells via autophagy, and its downstream mechanism remains unclear. Western blotting analyses and immunocytochemistry were applied to detect protein levels were detected in HUVECs. An in vitro scratch assay was used to detect cell migration...
January 29, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29354167/neonatal-severe-hyperparathyroidism-secondary-to-a-novel-homozygous-casr-gene-mutation
#10
Noman Ahmad, Mona Bahasan, Balgees Abdulhadi Abdullah Al-Ghamdi, Halah Faleh Al-Enizi, Ali Saeed Al-Zahrani
Neonatal severe hyperparathyroidism (NSHPT) is a rare autosomal recessive disease. Children present within the first 6 months of life and more commonly in the first few weeks. Common presentation is poor feeding, polyuria, dehydration, lethargy, failure to thrive, hypotonia, gastrointestinal dysmotility, osteopenia and symptoms of respiratory distress due to a poorly developed chest cage. We present a case of a 2-month old girl with severe hypercalcemia and hyperparathyroidism. She was found to have a novel homozygous mutation in the acceptor splicing site of intron 4 (c...
September 2017: Clinical Cases in Mineral and Bone Metabolism
https://www.readbyqxmd.com/read/29348629/the-suppressive-role-of-calcium-sensing-receptor-in-endometrial-cancer
#11
Xiaoyan Xin, Xianqin Zeng, Dilu Feng, Teng Hua, Shuangge Liu, Shuqi Chi, Qinghua Hu, Hongbo Wang
Studies have shown that calcium sensing receptor (CaSR) is involved in the progressions of several human cancers. However, the role of CaSR in endometrial cancer remains unknown. This study provides a preliminary analysis of the CaSR effect on endometrial cancer development. Ectopic CaSR expression by lentiviral transfection (CaSR-OV) in Ishikawa cells significantly increased intracellular calcium ([Ca2+]i) levels and cell apoptosis. E-cadherin and β-catenin expression and complex formation at the membrane were increased in CaSR-OV Ishikawa cells relative to control Ishikawa cells (vector)...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29345311/calcium-sensing-receptor-activates-the-nlrp3-inflammasome-in-ls14-preadipocytes-mediated-by-erk1-2-signaling
#12
Amanda D'Espessailles, Yuly A Mora, Cecilia Fuentes, Mariana Cifuentes
The study of the mechanisms that trigger inflammation in adipose tissue is key to understanding and preventing the cardiometabolic consequences of obesity. We have proposed a model where activation of the G protein-coupled calcium sensing receptor (CaSR) leads to inflammation and dysfunction in adipose cells. Upon activation, CaSR can mediate the expression and secretion of proinflammatory factors in human preadipocytes, adipocytes and adipose tissue explants. One possible pathway involved in CaSR-induced inflammation is the activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome, that promotes maturation and secretion of interleukin (IL)-1β...
January 18, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29335257/staphylococcal-superantigens-use-lama2-as-a-coreceptor-to-activate-t-cells
#13
Zhigang Li, Joseph J Zeppa, Mark A Hancock, John K McCormick, Terence M Doherty, Geoffrey N Hendy, Joaquín Madrenas
Canonical Ag-dependent TCR signaling relies on activation of the src-family tyrosine kinase LCK. However, staphylococcal superantigens can trigger TCR signaling by activating an alternative pathway that is independent of LCK and utilizes a Gα11-containing G protein-coupled receptor (GPCR) leading to PLCβ activation. The molecules linking the superantigen to GPCR signaling are unknown. Using the ligand-receptor capture technology LRC-TriCEPS, we identified LAMA2, the α2 subunit of the extracellular matrix protein laminin, as the coreceptor for staphylococcal superantigens...
January 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29325022/large-scale-exome-datasets-reveal-a-new-class-of-adaptor-related-protein-complex-2-sigma-subunit-ap2%C3%AF-mutations-located-at-the-interface-with-the-ap2-alpha-subunit-that-impair-calcium-sensing-receptor-signalling
#14
Caroline M Gorvin, Raghu Metpally, Victoria J Stokes, Fadil M Hannan, Sarath B Krishnamurthy, John D Overton, Jeffrey G Reid, Gerda E Breitwieser, Rajesh V Thakker
Mutations of the sigma subunit of the heterotetrameric adaptor-related protein complex 2 (AP2σ) impair signalling of the calcium-sensing receptor (CaSR), and cause familial hypocalciuric hypercalcaemia type 3 (FHH3). To date, FHH3-associated AP2σ mutations have only been identified at one residue, Arg15. We hypothesized that additional rare AP2σ variants may also be associated with altered CaSR function and hypercalcaemia, and sought for these by analysing >111,995 exomes (>60,706 from ExAc and dbSNP, and 51,289 from the Geisinger Health System-Regeneron DiscovEHR dataset which also contains clinical data)...
January 9, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29317227/prolonged-exposure-to-1-25-oh-2d3-and-high-ionized-calcium-induces-fgf-23-production-in-intestinal-epithelium-like-caco-2-monolayer-a-local-negative-feedback-for-preventing-excessive-calcium-transport
#15
Mayuree Rodrat, Kannikar Wongdee, Nattapon Panupinthu, Jirawan Thongbunchoo, Jarinthorn Teerapornpuntakit, Nateetip Krishnamra, Narattaphol Charoenphandhu
Overdose of oral calcium supplement and excessive intestinal calcium absorption can contribute pathophysiological conditions, e.g., nephrolithiasis, vascular calcification, dementia, and cardiovascular accident. Since our previous investigation has indicated that fibroblast growth factor (FGF)-23 could abolish the 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]-enhanced calcium absorption, we further hypothesized that FGF-23 produced locally in the enterocytes might be part of a local negative feedback loop to regulate calcium absorption...
January 6, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29284209/calcium-sensing-receptor-mediated-l-tryptophan-induced-secretion-of-cholecystokinin-and-glucose-dependent-insulinotropic-peptide-in-swine-duodenum
#16
Xiuying Zhao, Yihan Xian, Chao Wang, Liren Ding, Xianglong Meng, Weiyun Zhu, Suqin Hang
This study aimed to understand the effect of Tryptophan (Trp) on gut hormones secretion as well as the roles of the CaSR and its downstream signaling pathway in gut hormones secretion using swine duodenal perfusion in vitro. Swine duodenum was perfused with Krebs-Henseleit buffers (KHB) as a basal solution. Various concentrations (0, 10 mM and 20 mM) of Trp were applied to investigate the effect of Trp on gut hormones secretion. A CaSR antagonist was used to detect the involvement of CaSR and its signal molecules...
December 28, 2017: Journal of Veterinary Science
https://www.readbyqxmd.com/read/29247746/calcimimetic-r568-inhibits-tetrodotoxin-sensitive-colonic-electrolyte-secretion-and-reduces-c-fos-expression-in-myenteric-neurons
#17
Xiangrong Sun, Lieqi Tang, Steven Winesett, Wenhan Chang, Sam Xianjun Cheng
AIMS: Calcium-sensing receptor (CaSR) is expressed on neurons of both submucosal and myenteric plexuses of the enteric nervous system (ENS) and the CaSR agonist R568 inhibited Cl- secretion in intestine. The purpose of this study was to localize the primary site of action of R568 in the ENS and to explore how CaSR regulates secretion through the ENS. MATERIALS AND METHODS: Two preparations of rat proximal and distal colon were used. The full-thickness preparation contained both the submucosal and myenteric plexuses, whereas for the "stripped" preparation the myenteric plexus with the muscle layers was removed...
December 13, 2017: Life Sciences
https://www.readbyqxmd.com/read/29242120/osteoprotective-effects-of-salidroside-in-ovariectomized-mice-and-diabetic-mice
#18
Xiang-Fan Chen, Xiao-Li Li, Min Yang, Yan Song, Yan Zhang
Salidroside, an active constituent from the root of Rhodiola rosea L., has multiple pharmacological effects, such as anti-cancer, anti-inflammatory and anti-oxidative properties, etc. However, its protective effect on bone tissue via regulating calcium homeostasis is yet to be determined. This study was performed to investigate if salidroside could protect against bone injuries induced by estrogen deficiency or hyperglycemia through modulating calcium homeostasis. Ovariectomized (OVX) mice and diabetic mice were treated with salidroside (20mg/kg) for 6 weeks...
December 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29227550/live-cell-visualization-of-calcium-flux-in-vibratome-cut-thick-sections-of-viable-tumor-tissue
#19
James Koh, Joyce A Hogue, Julie A Sosa
This unit outlines a live-cell imaging approach developed for visualization of intracellular calcium flux in human parathyroid tumors following stimulation of the calcium-sensing receptor (CASR), a class C G protein-coupled receptor (GPCR). The primary assay readout, intracellular calcium release induced by activation of the inositol triphosphate receptor, is potentially generalizable to multiple other GPCR signaling events that utilize this common downstream signal transduction pathway. Advantages of the approach include: (1) preservation of native tissue context and positional information, allowing direct visualization of intratumoral functional heterogeneity; (2) quantitative documentation of reactivity to a physiological stimulus in an experimentally tractable ex vivo system; and (3) generation of a dynamic, functional classifier of tumor biochemical behavior to augment static marker assessment...
December 11, 2017: Current Protocols in Cell Biology
https://www.readbyqxmd.com/read/29212817/casr-signaling-down-regulates-aqp2-expression-via-a-novel-microrna-pathway-in-pendrin-and-nacl-cotransporter-knockout-mice
#20
Marianna Ranieri, Kamyar Zahedi, Grazia Tamma, Mariangela Centrone, Annarita Di Mise, Manoocher Soleimani, Giovanna Valenti
High concentrations of urinary calcium counteract vasopressin action via the activation of the calcium-sensing receptor (CaSR) that is expressed in the luminal membrane of collecting duct cells, which impairs the trafficking of aquaporin-2 (AQP2). Pendrin/NaCl cotransporter double-knockout (dKO) mice display significant calcium wasting and develop severe volume depletion, despite increased circulating vasopressin levels. We hypothesized that the CaSR-mediated impairment of AQP2 expression/trafficking underlies vasopressin resistance in dKO mice...
December 6, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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