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https://www.readbyqxmd.com/read/28633902/calcium-sensing-receptor-initiating-cystathionine-gamma-lyase-hydrogen-sulfide-pathway-to-inhibit-platelet-activation-in-hyperhomocysteinemia-rat
#1
Yuwen Wang, Ziqing Zhao, Sa Shi, Fei Gao, Jichao Wu, Shiyun Dong, Weihua Zhang, Yanhong Liu, Xin Zhong
Hyperhomocysteinemia (HHcy, high homocysteine) induces the injury of endothelial cells (ECs). Hydrogen sulfide (H2S) protects ECs and inhibits the activation of platelets. Calcium-sensing receptor (CaSR) regulates the production of endogenous H2S. However, whether CaSR inhibits the injury of ECs and the activation of platelets by regulating the endogenous cystathionine-gamma-lyase (CSE, a major enzyme that produces H2S)/H2S pathway in hyperhomocysteinemia has not been previously investigated. Here, we tested the ultrastructure alterations of ECs and platelets, the changes in the concentration of serum homocysteine and the parameters of blood of hyperhomocysteinemia rats were measured...
June 19, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28630081/calcium-sensing-receptor-genotype-and-response-to-cinacalcet-in-patients-undergoing-hemodialysis
#2
Sharon M Moe, Leah Wetherill, Brian Scott Decker, Dongbing Lai, Safa Abdalla, Jin Long, Matteo Vatta, Tatiana M Foroud, Glenn M Chertow
BACKGROUND AND OBJECTIVES: We tested the hypothesis that single nucleotide polymorphisms (SNPs) in the calcium-sensing receptor (CASR) alter the response to the calcimimetic cinacalcet. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We analyzed DNA samples in the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial, a randomized trial comparing cinacalcet to placebo on a background of usual care. Of the 3883 patients randomized, 1919 (49%) consented to DNA collection, and samples from 1852 participants were genotyped for 18 CASR polymorphisms...
June 19, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28623466/increases-in-circulating-amino-acids-with-in-feed-antibiotics-correlated-with-gene-expression-of-intestinal-amino-acid-transporters-in-piglets
#3
Miao Yu, Chunlong Mu, Yuxiang Yang, Chuanjian Zhang, Yong Su, Zan Huang, Kaifan Yu, Weiyun Zhu
In-feed antibiotics have been commonly used to promote the growth performance of piglets. The antibiotics can increase protein utilization, but the underlying mechanism is largely unknown. The present study investigated the effects of in-feed antibiotics on intestinal AA transporters and receptors to test the hypothesis that the alteration of circulating AA profiles may be concomitant with the change of intestinal AA transporters and receptors. Sixteen litters of piglets at day 7 started to receive creep feed with (Antibiotic) or without (Control) antibiotic...
June 16, 2017: Amino Acids
https://www.readbyqxmd.com/read/28615947/treatment-of-secondary-hyperparathyroidism-the-clinical-utility-of-etelcalcetide
#4
REVIEW
Mario Cozzolino, Andrea Galassi, Ferruccio Conte, Michela Mangano, Luca Di Lullo, Antonio Bellasi
Secondary hyperparathyroidism (SHPT), a very frequent, severe, and worsening complication of chronic kidney disease, is characterized by high serum parathyroid hormone (PTH), parathyroid gland hyperplasia, and disturbances in mineral metabolism. Clinically, SHPT shows renal osteodystrophy, vascular calcification, cardiovascular damage, and fatal outcome. Calcium-sensing receptor (CaSR) is the main physiological regulator of PTH secretion; its activation by calcium rapidly inhibits PTH. Another important player in regulating mineral metabolism is vitamin D receptor (VDR), which is under the influence of vitamin D and influences the intestinal absorption of calcium and phosphate, PTH gene expression, and bone calcium mobilization...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28609763/calcium-sensing-receptor-genetic-polymorphisms-and-risk-of-developing-nephrolithiasis-in-a-chinese-population
#5
Qi Ding, Bo Fan, Ying Shi, Zhijiang Fan, Li Ding, Feng Li, Wenjian Tu, Xiaohua Jin, Chao Qin, Qiang Cao, Qinbo Yuan, Jing Wang, Jun Ouyang
OBJECTIVE: To evaluate the association between calcium-sensing receptor (CaSR) Arg990Gly (rs1042636, A > G), Ala986Ser (rs1801725, G > T) polymorphisms, and urolithiasis risk. METHODS: Polymorphisms mentioned above were genotyped in a hospital-based case-control study of 615 patients diagnosed with nephrolithiasis and 315 kidney stone-free controls in a Chinese population using the SNaPshot method. RESULTS: The results indicated a significantly increased risk associated with CaSR Arg990Gly GG genotypes (OR 1...
June 14, 2017: Urologia Internationalis
https://www.readbyqxmd.com/read/28597792/implications-of-the-calcium-sensing-receptor-in-ischemia-reperfusion
#6
François Paquot, Justine Huart, Jean-Olivier Defraigne, Jean-Marie Krzesinski, François Jouret
The calcium-sensing receptor (CaSR) is a G protein-coupled receptor (GPCR) which was first isolated from bovine parathyroid glands. Its complex structure has been well characterized, which helped to better understand its function. The CaSR activity can be modulated by various ligands, either activators (also called "calcimimetics") or inhibitors (or "calcilytics"). The main role of the CaSR concerns Ca(2+) homeostasis. In bone, intestine and kidney, the CaSR acts as a sensor for extracellular ionized Ca(2+) concentration ([Ca(2+)]e) to keep it stable...
April 2017: Acta Cardiologica
https://www.readbyqxmd.com/read/28575322/mutant-mice-with-calcium-sensing-receptor-casr-activation-have-hyperglycemia-that-is-rectified-by-calcilytic-therapy
#7
Valerie N Babinsky, Fadil M Hannan, Reshma D Ramracheya, Quan Zhang, M Andrew Nesbit, Alison Hugill, Liz Bentley, Tertius A Hough, Elizabeth Joynson, Michelle Stewart, Abhishek Aggarwal, Maximilian Prinz-Wohlgenannt, Caroline M Gorvin, Enikö Kallay, Sara Wells, Roger D Cox, Duncan Richards, Patrik Rorsman, Rajesh V Thakker
The calcium-sensing receptor (CaSR) is a family C G-protein-coupled receptor (GPCR) that plays a pivotal role in extracellular calcium homeostasis. The CaSR is also highly expressed in pancreatic islet α- and β-cells that secrete glucagon and insulin, respectively. To determine whether the CaSR may influence systemic glucose homeostasis, we characterized a mouse model with a germline gain-of-function CaSR mutation, Leu723Gln, referred to as Nuclear flecks (Nuf). Heterozygous- (CasrNuf/+) and homozygous-affected (CasrNuf/Nuf) mice were shown to have hypocalcemia in association with impaired glucose tolerance and insulin secretion...
June 2, 2017: Endocrinology
https://www.readbyqxmd.com/read/28518143/calcium-sensing-receptor-protects-high-glucose-induced-energy-metabolism-disorder-via-blocking-gp78-ubiquitin-proteasome-pathway
#8
Yuehong Wang, Ping Gao, Can Wei, Hongzhu Li, Li Zhang, Yajun Zhao, Bo Wu, Ye Tian, Weihua Zhang, Lingyun Wu, Rui Wang, Changqing Xu
Diabetic cardiomyopathy (DCM) is a major complication and fatal cause of the patients with diabetes. The calcium sensing receptor (CaSR) is a G protein-coupled receptor, which is involved in maintaining calcium homeostasis, regulating cell proliferation and apoptosis, and so on. In our previous study, we found that CaSR expression, intracellular calcium levels and cardiac function were all significantly decreased in DCM rats; however, the exact mechanism are not clear yet. The present study revealed the protective role of CaSR in myocardial energy metabolism disorder induced by high glucose (HG) as well as the underlying mechanism...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28515208/glucocorticoid-responsive-lymphocytic-parathyroiditis-and-hypocalciuric-hypercalcemia-due-to-autoantibodies-against-the-calcium-sensing-receptor-a-case-report-and-literature-review
#9
Li Song, Liping Liu, R Tyler Miller, Shirley X Yan, Nancy Jackson, Shelby A Holt, Naim M Maalouf
OBJECTIVE: Autoimmune lymphocytic parathyroiditis and acquired hypocalciuric hypercalcemia associated with autoantibodies against the calcium-sensing receptor (anti-CaSR) are rare and poorly understood conditions. Here, we describe a patient with acquired parathyroid hormone (PTH)-dependent hypercalcemia with associated hypocalciuria, found to have true lymphocytic parathyroiditis on histopathology, and circulating anti-CaSR antibodies in serum. DESIGN AND METHODS: A 64-year-old woman was referred to our clinic for persistent hypercalcemia after a subtotal parathyroidectomy...
July 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28508378/population-pharmacokinetic-and-pharmacodynamic-modeling-of-etelcalcetide-in-patients-with-chronic-kidney-disease-and-secondary-hyperparathyroidism-receiving-hemodialysis
#10
Ping Chen, Adimoolam Narayanan, Benjamin Wu, Per Olsson Gisleskog, John P Gibbs, Andrew T Chow, Murad Melhem
INTRODUCTION: Etelcalcetide is a novel calcimimetic that binds and activates calcium-sensing receptors (CaSRs) for the treatment of secondary hyperparathyroidism (SHPT). METHODS: To assess titrated dosing regimens, population pharmacokinetic (PK) and PK/pharmacodynamic (PKPD) modeling of etelcalcetide was performed using NONMEM 7.2. In this analysis, plasma etelcalcetide, serum parathyroid hormone (PTH) and calcium (Ca) concentration-time data were collected from five phase I, II, and III clinical trials following single or multiple intravenous doses of etelcalcetide ranging from 2...
May 15, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28506888/calcium-sensing-receptor-erk-signaling-promotes-odontoblastic-differentiation-of-human-dental-pulp-cells
#11
Hiroyuki Mizumachi, Shinichiro Yoshida, Atsushi Tomokiyo, Daigaku Hasegawa, Sayuri Hamano, Asuka Yuda, Hideki Sugii, Suguru Serita, Hiromi Mitarai, Katsuaki Koori, Naohisa Wada, Hidefumi Maeda
Activation of the G protein-coupled calcium-sensing receptor (CaSR) has crucial roles in skeletal development and bone turnover. Our recent study has identified a role for activated CaSR in the osteogenic differentiation of human periodontal ligament stem cells. Furthermore, odontoblasts residing inside the tooth pulp chamber play a central role in dentin formation. However, it remains unclear how CaSR activation affects the odontoblastic differentiation of human dental pulp cells (HDPCs). We have investigated the odontoblastic differentiation of HDPCs exposed to elevated levels of extracellular calcium (Ca) and strontium (Sr), and the contribution of CaSR and the L-type voltage-dependent calcium channel (L-VDCC) to this process...
May 12, 2017: Bone
https://www.readbyqxmd.com/read/28498361/rectal-cancer-in-a-patient-with-bartter-syndrome-a-case-report
#12
Shiki Fujino, Norikatsu Miyoshi, Masayuki Ohue, Mikio Mukai, Yoji Kukita, Taishi Hata, Chu Matsuda, Tsunekazu Mizushima, Yuichiro Doki, Masaki Mori
A woman with rectal cancer was scheduled for surgery. However, she also had hypokalemia, hyperreninemia, and hyperaldosteronism in the absence of any known predisposing factors or endocrine tumors. She was given intravenous potassium, and her blood abnormalities stabilized after tumor resection. Genetic analysis revealed mutations in several genes associated with Bartter syndrome (BS) and Gitelman syndrome, including SLC12A1, CLCNKB, CASR, SLC26A3, and SLC12A3. Prostaglandin E2 (PGE2) plays an important role in BS and worsens electrolyte abnormalities...
May 12, 2017: Genes
https://www.readbyqxmd.com/read/28473749/amyloid-%C3%AE-exposed-human-astrocytes-overproduce-phospho-tau-and-overrelease-it-within-exosomes-effects-suppressed-by-calcilytic-nps-2143-further-implications-for-alzheimer-s-therapy
#13
Anna Chiarini, Ubaldo Armato, Emanuela Gardenal, Li Gui, Ilaria Dal Prà
The two main drivers of Alzheimer's disease (AD), amyloid-β (Aβ) and hyperphosphorylated Tau (p-Tau) oligomers, cooperatively accelerate AD progression, but a hot debate is still ongoing about which of the two appears first. Here we present preliminary evidence showing that Tau and p-Tau are expressed by untransformed cortical adult human astrocytes in culture and that exposure of such cells to an Aβ42 proxy, Aβ25-35, which binds the calcium-sensing receptor (CaSR) and activates its signaling, significantly increases intracellular p-Tau levels, an effect CaSR antagonist (calcilytic) NPS 2143 wholly hinders...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28460682/role-of-the-calcium-sensing-receptor-casr-in-bovine-gametes-and-during-in%C3%A2-vitro-fertilization
#14
Beatriz Macías-García, Graça Lopes, Antonio Rocha, Lauro González-Fernández
Calcium Sensing Receptor (CaSR) is a G-protein coupled receptor which senses extracellular calcium and activates diverse intracellular pathways. The objective of our work was to demonstrate the presence of CaSR in bovine gametes and its possible role in fertilization and embryo development. The location of CaSR was demonstrated by immunofluorescence in bovine gametes; additionally bovine sperm were incubated with 5, 10 and 15 μM of the specific CaSR inhibitor NPS2143 in a Tyrode's Albumin Lactate Pyruvate medium (4 h)...
June 2017: Theriogenology
https://www.readbyqxmd.com/read/28455519/calcium-sensing-receptor-antagonist-nps-2143-restores-amyloid-precursor-protein-physiological-non-amyloidogenic-processing-in-a%C3%AE-exposed-adult-human-astrocytes
#15
Anna Chiarini, Ubaldo Armato, Daisong Liu, Ilaria Dal Prà
Physiological non-amyloidogenic processing (NAP) of amyloid precursor holoprotein (hAPP) by α-secretases (e.g., ADAM10) extracellularly sheds neurotrophic/neuroprotective soluble (s)APPα and precludes amyloid-β peptides (Aβs) production via β-secretase amyloidogenic processing (AP). Evidence exists that Aβs interact with calcium-sensing receptors (CaSRs) in human astrocytes and neurons, driving the overrelease of toxic Aβ42/Aβ42-os (oligomers), which is completely blocked by CaSR antagonist (calcilytic) NPS 2143...
April 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28454088/overexpression-of-a-functional-calcium-sensing-receptor-dramatically-increases-osteolytic-potential-of-mda-mb-231-cells-in-a-mouse-model-of-bone-metastasis-through-epiregulin-mediated-osteoprotegerin-downregulation
#16
Cédric Boudot, Lucie Hénaut, Ursula Thiem, Sandra Geraci, Mariangela Galante, Paulo Saldanha, Zuzana Saidak, Isabelle Six, Philippe Clézardin, Said Kamel, Romuald Mentaverri
INTRODUCTION AND AIMS: Osteolytic bone metastases are observed in advanced cases of breast cancer. In vitro data suggest that the activity of the calcium-sensing receptor (CaSR) expressed by metastatic cells could potentiate their osteolytic potential. This study aimed to demonstrate in vivo the involvement of the CaSR in breast cancer cells osteolytic potential and to identify potential targets linked to CaSR activity. METHODS AND RESULTS: MDA-MB-231 stably transfected with plasmids containing either a full-length wild-type CaSR (CaSR-WT), or a functionally inactive dominant negative mutant (CaSR-DN) or an empty vector (EV) were intratibially injected into Balb/c-Nude mice...
April 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28450119/role-of-the-calcium-sensing-receptor-in-cardiomyocyte-apoptosis-via-mitochondrial-dynamics-in-compensatory-hypertrophied-myocardium-of-spontaneously-hypertensive-rat
#17
Siting Hong, Xin Zhang, Xiaohui Zhang, Wenxiu Liu, Yu Fu, Yue Liu, Zhiyu Shi, Jinyu Chi, Meng Zhao, Xinhua Yin
Calcium sensing receptor (CaSR) mediates pathological cardiac hypertrophy. Mitochondria maintain their function through fission and fusion and disruption of mitochondrial dynamic is linked to various cardiac diseases. This study examined how inhibition of CaSR by the inhibitor Calhex231 affected the mitochondrial dynamics in a hypertensive model in rats. Spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) rats were used in this study. Cardiac function and blood pressure was evaluated at the end of the study...
June 3, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28444561/a-rare-variant-in-the-fhl1-gene-associated-with-x-linked-recessive-hypoparathyroidism
#18
Nir Pillar, Oren Pleniceanu, Mingyan Fang, Limor Ziv, Einat Lahav, Shay Botchan, Le Cheng, Benjamin Dekel, Noam Shomron
Isolated familial hypoparathyroidism is an extremely rare disorder, which to date has been linked to several loci including mutations in CASR, GCM2, and PTH, as well as a rare condition defined as X-linked recessive hypoparathyroidism, previously associated with a 1.5 Mb region on Xq26-q27. Here, we report a patient with hypocalcemia-induced seizures leading to the diagnosis of primary hypoparathyroidism. Mutations in CASR, GCM2, and PTH were ruled out, while whole exome sequencing of the family suggested FHL1, located on chromosome Xq26, as the most likely causative gene variant (FHL1, exon 4, c...
April 25, 2017: Human Genetics
https://www.readbyqxmd.com/read/28422826/idiopathic-hypoparathyroidism-with-extensive-intracranial-calcification-in-children-first-report-from-saudi-arabia
#19
Naglaa M Kamal, Hamed A Alghamdi, Abdulrahman A Halabi, Ayman A Bakkar, Ali Algarni, Abdullah Alharbi, Abdulla A Alharthi, Rawan A Alharbi, Laila M Sherief
RATIONALE: Pediatric idiopathic hypoparathyroidism with extensive intracranial calcifications outside the basal ganglia (BG) is extremely rare with less than 10 cases worldwide. PATIENT CONCERNS: An 11-year-old Saudi male child presented with tetany with otherwise normal neurological and other body system examination diagnoses severe hypocalcemia for differential diagnosis. INTERVENTIONS: Further investigations revealed hyperphosphatemia and undetectable serum intact parathyroid hormone...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28419469/the-endoplasmic-reticulum-associated-protein-os-9-behaves-as-a-lectin-in-targeting-the-immature-calcium-sensing-receptor
#20
Bryan K Ward, Sarah L Rea, Aaron L Magno, Bernadette Pedersen, Suzanne J Brown, Shelby Mullin, Ajanthy Arulpragasam, Evan Ingley, Arthur D Conigrave, Thomas Ratajczak
The mechanisms responsible for the processing and quality control of the calcium-sensing receptor (CaSR) in the endoplasmic reticulum (ER) are largely unknown. In a yeast two-hybrid screen of the CaSR C-terminal tail (residues 865 -1078), we identified osteosarcoma-9 (OS-9) protein as a binding partner. OS-9 is an ER-resident lectin that targets misfolded glycoproteins to the ER-associated degradation (ERAD) pathway through recognition of specific N-glycans by its mannose-6-phosphate receptor homology (MRH) domain...
April 17, 2017: Journal of Cellular Physiology
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