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https://www.readbyqxmd.com/read/28445755/mapping-ryanodine-binding-sites-in-the-pore-cavity-of-ryanodine-receptors
#1
Van A Ngo, Laura L Perissinotti, Williams Miranda, S R Wayne Chen, Sergei Y Noskov
Ryanodine (Ryd) irreversibly targets ryanodine receptors (RyRs), a family of intracellular calcium release channels essential for many cellular processes ranging from muscle contraction to learning and memory. Little is known of the atomistic details about how Ryd binds to RyRs. In this study, we used all-atom molecular dynamics simulations with both enhanced and bidirectional sampling to gain direct insights into how Ryd interacts with major residues in RyRs that were experimentally determined to be critical for its binding...
April 25, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28445391/telomerase-inhibitory-effects-of-red-pigment-rubropunctatin-and-statin-monacolin-l-isolated-from-red-yeast-rice
#2
Baojun Xu, Qijun Wang, Changkeun Sung
In addition to the cholesterol-lowering activity of red yeast rice (RYR), its anticancer activities have been frequently reported. However, the mechanism of action of the anticancer activity of RYR is not yet fully understood. The objective of the current study was to elucidate anticancer compositions and anticancer mechanism of actions of RYR. The isolated compounds from RYR were subjected to anti-proliferation assay, apoptosis assay via flow cytometry, and telomerase inhibitory assay via telomeric repeat amplification protocol-PCR (TRAP-PCR) assay, and Western blotting assay in an in vitro cell culture system...
April 26, 2017: Genes
https://www.readbyqxmd.com/read/28390800/ca-2-release-via-two-pore-channel-type-2-tpc2-is-required-for-slow-muscle-cell-myofibrillogenesis-and-myotomal-patterning-in-intact-zebrafish-embryos
#3
Jeffrey J Kelu, Sarah E Webb, John Parrington, Antony Galione, Andrew L Miller
We recently demonstrated a critical role for two-pore channel type 2 (TPC2)-mediated Ca(2+) release during the differentiation of slow (skeletal) muscle cells (SMC) in intact zebrafish embryos, via the introduction of a translational-blocking morpholino antisense oligonucleotide (MO). Here, we extend our study and demonstrate that knockdown of TPC2 with a non-overlapping splice-blocking MO, knockout of TPC2 (via the generation of a tpcn2(dhkz1a) mutant line of zebrafish using CRISPR/Cas9 gene-editing), or the pharmacological inhibition of TPC2 action with bafilomycin A1 or trans-ned-19, also lead to a significant attenuation of SMC differentiation, characterized by a disruption of SMC myofibrillogenesis and gross morphological changes in the trunk musculature...
April 6, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28387457/dampened-activity-of-ryanodine-receptor-channels-in-mutant-skeletal-muscle-lacking-tric-a
#4
Sam El-Ajouz, Elisa Venturi, Katja Witschas, Matthew Beech, Abigail D Wilson, Chris Lindsay, David Eberhardt, Fiona O'Brien, Tsunaki Iida, Miyuki Nishi, Hiroshi Takeshima, Rebecca Sitsapesan
TRIC-A is a major component of the nuclear and sarcoplasmic reticulum (SR) membranes of cardiac and skeletal muscle, and is localised closely with RyR channels in the SR terminal cisternae. The skeletal muscle of Tric-a KO mice is characterised by Ca(2+) overloaded and swollen SR and by changes in the properties of SR Ca(2+) release. We therefore investigated if RyR1 gating behaviour is modified in the SR from Tric-a KO mice by incorporating native RyR1 into planar phospholipid bilayers under voltage-clamp conditions...
April 7, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28384221/kchip2-regulates-the-cardiac-ca2-transient-and-myocyte-contractility-by-targeting-ryanodine-receptor-activity
#5
Drew M Nassal, Xiaoping Wan, Haiyan Liu, Kenneth R Laurita, Isabelle Deschênes
Pathologic electrical remodeling and attenuated cardiac contractility are featured characteristics of heart failure. Coinciding with these remodeling events is a loss of the K+ channel interacting protein, KChIP2. While, KChIP2 enhances the expression and stability of the Kv4 family of potassium channels, leading to a more pronounced transient outward K+ current, Ito,f, the guinea pig myocardium is unique in that Kv4 expression is absent, while KChIP2 expression is preserved, suggesting alternative consequences to KChIP2 loss...
2017: PloS One
https://www.readbyqxmd.com/read/28373957/comparative-study-the-expression-of-calcium-cycling-genes-in-bombay-duck-harpadon-nehereus-and-beltfish-trichiurus-lepturus-with-different-swimming-activities
#6
Hui Zhang, Gilbert Audira, Yuan Li, Weiwei Xian, Muhammed Muhsin Varikkodan, Chung-Der Hsiao
The contraction and relaxation events of the muscle is mediated by the coordination of many important calcium cycling proteins of ryanodine receptor (RYR), troponin C (TNNC), parvalbumin (PVALB), sarcoendoplasmic reticulum calcium transport ATPase (SERCA) and calsequestrin (CASQ). In higher vertebrates, the expression level of calcium cycling proteins are positively correlated to the muscle contraction/relaxation ability of the cell. In this study, we used RNAseq to explore the expression profile of calcium cycling genes between two marine fish of Bombay duck (Harpadon nehereus) and beltfish (Trichiurus lepturus) with poor and robust swimming activities, respectively...
June 2017: Genomics Data
https://www.readbyqxmd.com/read/28373535/dantrolene-requires-mg-2-to-arrest-malignant-hyperthermia
#7
Rocky H Choi, Xaver Koenig, Bradley S Launikonis
Malignant hyperthermia (MH) is a clinical syndrome of skeletal muscle that presents as a hypermetabolic response to volatile anesthetic gases, where susceptible persons may develop lethally high body temperatures. Genetic predisposition mainly arises from mutations on the skeletal muscle ryanodine receptor (RyR). Dantrolene is administered to alleviate MH symptoms, but its mechanism of action and its influence on the Ca(2+) transients elicited by MH triggers are unknown. Here, we show that Ca(2+) release in the absence of Mg(2+) is unaffected by the presence of dantrolene but that dantrolene becomes increasingly effective as cytoplasmic-free [Mg(2+)] (free [Mg(2+)]cyto) passes mM levels...
April 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28364296/juvenile-onset-myasthenia-gravis-autoantibody-status-clinical-characteristics-and-genetic-polymorphisms
#8
Yu Hong, Geir Olve Skeie, Paraskevi Zisimopoulou, Katerina Karagiorgou, Socrates J Tzartos, Xiang Gao, Yao-Xian Yue, Fredrik Romi, Xu Zhang, Hai-Feng Li, Nils Erik Gilhus
Myasthenia gravis (MG) is an autoimmune disorder mediated by antibodies against proteins at the neuromuscular junction. Juvenile-onset MG (JMG) has been reported to have special characteristics. It is still unclear whether there are any pathogenic and genetic differences between juvenile and adult MG. In this study, we evaluated the clinical characteristics, autoantibody status (antibodies against AChR, MuSK, LRP4, titin and RyR) and genetic susceptibility (CHRNA1, CTLA4 and AIRE) in 114 Chinese JMG patients, and compared with 207 young adult MG patients (onset age 18-40 years)...
March 31, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28337264/ip3r-and-ryr-calcium-channels-are-involved-in-neonatal-rat-cardiac-myocyte-hypertrophy-induced-by-tumor-necrosis-factor-%C3%AE
#9
Gui-Jun Wang, Lian-Yi Guo, Hong-Xin Wang, Yu-Sheng Yao
To investigate which calcium channels are involved in cardiac myocyte hypertrophy induced by TNF-α, cultured cardiomyocytes were treated with 100 μg/L TNF-α. In addition, three different calcium channel blockers (2-APB, ryanodine and nifedipine) were used, and the effects of each calcium channel blocker on cardiac hypertrophy induced by TNF-α were carefully observed. Measurements included cytosolic calcium transients ([Ca(2+)]i), the level of intracellular calcium in individual cells, cell protein content, cell protein synthesis and cell volume...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28333380/smooth-muscle-ion-channels-and-regulation-of-vascular-tone-in-resistance-arteries-and-arterioles
#10
Nathan R Tykocki, Erika M Boerman, William F Jackson
Vascular tone of resistance arteries and arterioles determines peripheral vascular resistance, contributing to the regulation of blood pressure and blood flow to, and within the body's tissues and organs. Ion channels in the plasma membrane and endoplasmic reticulum of vascular smooth muscle cells (SMCs) in these blood vessels importantly contribute to the regulation of intracellular Ca2+ concentration, the primary determinant of SMC contractile activity and vascular tone. Ion channels provide the main source of activator Ca2+ that determines vascular tone, and strongly contribute to setting and regulating membrane potential, which, in turn, regulates the open-state-probability of voltage gated Ca2+ channels (VGCCs), the primary source of Ca2+ in resistance artery and arteriolar SMCs...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28322744/basal-ryanodine-receptor-activity-suppresses-autophagic-flux
#11
Tim Vervliet, Isabel Pintelon, Kirsten Welkenhuyzen, Martin D Bootman, Hiroko Bannai, Katsuhiko Mikoshiba, Wim Martinet, Nael Nadif Kasri, Jan B Parys, Geert Bultynck
The inositol 1,4,5-trisphosphate receptors (IP3Rs) and intracellular Ca(2+) signaling are critically involved in regulating different steps of autophagy, a lysosomal degradation pathway. The ryanodine receptors (RyR), intracellular Ca(2+)-release channels mainly expressed in excitable cell types including muscle and neurons, have however not yet been extensively studied in relation to autophagy. Yet, aberrant expression and excessive activity of RyRs in these tissues has been implicated in the onset of several diseases including Alzheimer's disease, where impaired autophagy regulation contributes to the pathology...
March 18, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28316566/blockade-of-ryrs-in-the-er-attenuates-6-ohda-induced-calcium-overload-cellular-hypo-excitability-and-apoptosis-in-dopaminergic-neurons
#12
Lu Huang, Ying Xue, DaYun Feng, RuiXin Yang, Tiejian Nie, Gang Zhu, Kai Tao, GuoDong Gao, Qian Yang
Calcium (Ca(2+)) dyshomeostasis induced by endoplasmic reticulum (ER) stress is an important molecular mechanism of selective dopaminergic (DA) neuron loss in Parkinson's disease (PD). Inositol 1,4,5-triphosphate receptors (IP3Rs) and ryanodine receptors (RyRs), which are located on the ER surface, are the main endogenous Ca(2+) release channels and play crucial roles in regulating Ca(2+) homeostasis. However, the roles of these endogenous Ca(2+) release channels in PD and their effects on the function and survival of DA neurons remain unknown...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28303572/intracellular-calcium-release-channels-an-update
#13
Gaetano Santulli, Ryutaro Nakashima, Qi Yuan, Andrew R Marks
Ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP3Rs) are calcium (Ca(2+) ) release channels on the endo/sarcoplasmic reticulum (ER/SR). Here we summarize the latest advances in the field, describing the recently discovered mechanistic roles of intracellular Ca(2+) release channels in the regulation of mitochondrial fitness and endothelial function, providing novel therapeutic options for the treatment of heart failure, hypertension, and diabetes mellitus. This article is protected by copyright...
March 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28292875/in-vivo-ca-2-dynamics-induced-by-ca-2-injection-in-individual-rat-skeletal-muscle-fibers
#14
Mario Wakizaka, Hiroaki Eshima, Yoshinori Tanaka, Hideki Shirakawa, David C Poole, Yutaka Kano
In contrast to cardiomyocytes, store overload-induced calcium ion (Ca(2+)) release (SOICR) is not considered to constitute a primary Ca(2+) releasing system from the sarcoplasmic reticulum (SR) in skeletal muscle myocytes. In the latter, voltage-induced Ca(2+) release (VICR) is regarded as the dominant mechanism facilitating contractions. Any role of the SOICR in the regulation of cytoplasmic Ca(2+) concentration ([Ca(2+)]i) and its dynamics in skeletal muscle in vivo remains poorly understood. By means of in vivo single fiber Ca(2+) microinjections combined with bioimaging techniques, we tested the hypothesis that the [Ca(2+)]i dynamics following Ca(2+) injection would be amplified and fiber contraction facilitated by SOICR...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28277227/-red-yeast-rice-induced-muscular-injuries-analysis-of-french-pharmacovigilance-database-and-literature-review
#15
Christelle Philibert, Virginie Bres, Marie-Josèphe Jean-Pastor, Claire Guy, Bénédicte Lebrun-Vignes, Perrine Robin, Véronique Pinzani, Dominique Hillaire-Buys
Red yeast rice (RYR) is a dietary supplement containing monacolins obtained by fermentation of Monascus purpureus strains. Because of its structural homology with lovastatin, monacolin K inhibits HMG-CoA reductase and shows hypocholesterolemic properties comparable to synthetic statins. We studied all cases of myopathy involving RYR reported in the French national pharmacovigilance database (6 cases) and in scientific literature (9 cases). Among these cases, 9 showed elevated creatine kinase, 3 rhabdomyolysis and 2 myalgia...
October 27, 2016: Thérapie
https://www.readbyqxmd.com/read/28257063/red-yeast-rice
#16
Thu Nguyen, Mitchell Karl, Antonello Santini
Red yeast rice (RYR), produced by the fermentation of the Monascus purpureus mold, has been used for a long time in Asian cuisine and traditional medicine. It consists of multiple bioactive substances, including monacolins, which potentially can be used as a nutraceutical. Monacolin K, which is chemically identical to lovastatin, has been recognized as responsible for the cholesterolreducing effect of this compound. While the European Food Safety Authority maintains that the use of monacolin K from RYR preparations of at least 10 mg can produce a normal blood cholesterol level, the United States Food and Drug Administration considers monacolin K, due to its similarity with lovastatin, an unapproved drug, and therefore marketing of products that label the monacolin content is prohibited...
March 1, 2017: Foods (Basel, Switzerland)
https://www.readbyqxmd.com/read/28242257/exendin-4-inhibits-structural-remodeling-and-improves-ca-2-homeostasis-in-rats-with-heart-failure-via-the-glp-1-receptor-through-the-enos-cgmp-pkg-pathway
#17
Jingjing Chen, Dandan Wang, Fangai Wang, Shaobo Shi, Yuting Chen, Bo Yang, Yanhong Tang, Congxin Huang
The glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 is a long-acting analog of GLP-1, which stimulates insulin secretion and is clinically used in the treatment of type 2 diabetes. Previous studies have demonstrated that GLP-1 agonists and analogs serve as cardioprotective factors in various conditions. Disturbances in calcium cycling are characteristic of heart failure (HF); therefore, the aim of this study was to investigate the effect of exendin-4 (a GLP-1 mimetic) on the regulation of calcium handling and to identify the underlying mechanisms in an HF rat model after myocardial infarction (MI)...
April 2017: Peptides
https://www.readbyqxmd.com/read/28237334/functional-involvement-of-protein-kinase-c-rho-kinase-and-trpc3-decreases-while-plc-increases-with-advancement-of-pregnancy-in-mediating-oxytocin-induced-myometrial-contractions-in-water-buffaloes-bubalus-bubalis
#18
Abhishek Sharma, Udayraj P Nakade, Soumen Choudhury, Satish Kumar Garg
Present study unravels the involvement of different calcium signaling pathways in oxytocin-induced contractions in myometrium of non-pregnant and pregnant buffaloes during early and mid-pregnancy stages. Uteri of pregnant animals were more sensitive than of non-pregnant buffaloes. Phasic contractions and frequency of contraction significantly increased with advancement of pregnancy, while tonic contractions non-significantly and amplitude significantly decreased from six months pregnancy onward. Oxytocin produced concentration-dependent-contraction on isolated myometrial strips of pregnant and non-pregnant buffaloes and the dose response curves (DRCs) of oxytocin were significantly (P < 0...
April 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28181698/calcium-uptake-via-mitochondrial-uniporter-contributes-to-palmitic-acid-induced-apoptosis-in-mouse-podocytes
#19
Zeting Yuan, Aili Cao, Hua Liu, Hengjiang Guo, Yingjun Zang, Yi Wang, Yunman Wang, Hao Wang, Peihao Yin, Wen Peng
Podocytes are component cells of the glomerular filtration barrier, and their loss by apoptosis is the main cause of proteinuria that leads to diabetic nephropathy (DN). Therefore, insights into podocyte apoptosis mechanism would allow a better understanding of DN pathogenesis and thus help develop adequate therapeutic strategies. Here, we investigated the molecular mechanism of palmitic acid-inhibited cell death in mouse podocytes, and found that palmitic acid increased cell death in a dose- and time-dependent manner...
February 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28169003/increased-calcium-leak-associated-with-reduced-calsequestrin-expression-in-hyperthyroid-cardiomyocytes
#20
David R de Alba-Aguayo, Natalia Pavón, Martha Mercado-Morales, Miyamin Miranda-Saturnino, Mavil López-Casamichana, Agustin Guerrero-Hernández, Angelica Rueda
INTRODUCTION: Calcium (Ca(2+)) leak during cardiac diastole is chiefly mediated by intracellular Ca(2+) channel/Ryanodine Receptors. Increased diastolic Ca(2+) leak has been proposed as the mechanism underlying the appearance of hereditary arrhythmias. However, little is known about alterations in diastolic Ca(2+) leak and the specific roles played by key intracellular Ca(2+)-handling proteins in hyperthyroidism, a known arrhythmogenic condition. AIM: We sought to determine whether there were modifications in diastolic Ca(2+) leak, based on the recording of Ca(2+) sparks and Ca(2+) waves; we also investigated changes in the expression and activity of key Ca(2+) handling proteins, including ryanodine receptors, Sarco-Endoplasmic Reticulum Ca(2+) ATPase pump and calsequestrin in isolated left-ventricular cardiomyocytes isolated from hyperthyroid rats...
January 23, 2017: Cell Calcium
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