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"ryanodine receptor" OR "ryr" OR "ryr2"

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https://www.readbyqxmd.com/read/29154060/efficacy-and-safety-of-a-combination-of-red-yeast-rice-and-olive-extract-in-hypercholesterolemic-patients-with-and-without-statin-associated-myalgia
#1
Christian Tshongo Muhindo, Sylvie A Ahn, Michel F Rousseau, Yvan Dierckxsens, Michel P Hermans
Cholesfytol(®), a lipid-lowering dietary supplement with antioxidant and anti-atherosclerotic properties, combines red yeast rice (RYR) and olive extract (5mg hydroxytyrosol equivalent) and represents an alternative for patients who do not wish or are unable to use chemical statins, including individuals with previous statin-associated muscle symptoms (SAMS). A 2-months observational non-randomized study was performed to evaluate the efficacy, tolerance and safety of Cholesfytol(®) (1 tablet/day) in 642 hypercholesterolemic patients (mean age: 59 yrs; total cholesterol (TC) ≥200; LDL-C ≥140mg/dl)...
December 2017: Complementary Therapies in Medicine
https://www.readbyqxmd.com/read/29151485/evolution-of-vertebrate-ryanodine-receptors-family-in-relation-to-functional-divergence-and-conservation
#2
Zhiwen Ding, Juan Peng, Yanyan Liang, Chunjie Yang, Guoliang Jiang, Jun Ren, Yunzeng Zou
Ryanodine receptors (RyRs), the large homotetrameric protein complexes, regulate the release of calcium from intracellular stores into the cytosol and play vital roles in the excitation-contraction coupling of cells. However, the evolutionary relationship of RyRs in vertebrates has yet to be elucidated. We identified 22 RyRs from Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Anolis carolinensis, Rana catesbeiana, and Danio rerio. The phylogenetic relationship, motifs analysis and reconstruction of ancestral RyRs showed that the members of RyR family in vertebrates were grouped into three clades: the RyR1 clade, the RyR2 clade, and the RyR3 clade...
November 17, 2017: International Heart Journal
https://www.readbyqxmd.com/read/29150445/the-antiapoptotic-protein-hax-1-mediates-half-of-phospholamban-s-inhibitory-activity-on-calcium-cycling-and-contractility-in-the-heart
#3
Philip A Bidwell, Kobra Haghighi, Evangelia G Kranias
The antiapoptotic protein HS-associated protein X-1 (HAX-1) localizes to sarcoplasmic reticulum (SR) in the heart and interacts with the small membrane protein phospholamban (PLN), inhibiting the cardiac sarco/endoplasmic reticulum calcium ATPase (SERCA2a) in the regulation of overall calcium handling and heart muscle contractility. However, because global HAX-1 deletion causes early lethality, how much endogenous HAX-1 contributes to PLN's inhibitory activity on calcium cycling is unknown. We therefore generated a cardiac-specific and inducible knockout mouse model...
November 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29150444/toll-like-receptor-4-induced-ryanodine-receptor-2-oxidation-and-sarcoplasmic-reticulum-ca2-leakage-promote-cardiac-contractile-dysfunction-in-sepsis
#4
Jie Yang, Rui Zhang, Xin Jiang, Jingzhang Lv, Ying Li, Hongyu Ye, Wenjuan Liu, Gang Wang, Cuicui Zhang, Na Zheng, Ming Dong, Yan Wang, Peiya Chen, Kumar Santosh, Yong Jiang, Jie Liu
Studies suggest the potential role of sarcoplasmic reticulum (SR) Ca2+ leak in cardiac contractile dysfunction in sepsis. However, direct supporting evidence is lacking, and the mechanisms underlying this SR leak are poorly understood. Here, we investigated the changes in cardiac Ca2+ handling and contraction in LPS-treated rat cardiomyocytes and a mouse model of polymicrobial sepsis produced by cecal ligation and puncture (CLP). LPS decreased the systolic Ca2+ transient and myocyte contraction, as well as SR Ca2+ content...
November 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29145393/estimating-the-probabilities-of-rare-arrhythmic-events-in-multiscale-computational-models-of-cardiac-cells-and-tissue
#5
Mark A Walker, Viatcheslav Gurev, John J Rice, Joseph L Greenstein, Raimond L Winslow
Ectopic heartbeats can trigger reentrant arrhythmias, leading to ventricular fibrillation and sudden cardiac death. Such events have been attributed to perturbed Ca2+ handling in cardiac myocytes leading to spontaneous Ca2+ release and delayed afterdepolarizations (DADs). However, the ways in which perturbation of specific molecular mechanisms alters the probability of ectopic beats is not understood. We present a multiscale model of cardiac tissue incorporating a biophysically detailed three-dimensional model of the ventricular myocyte...
November 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29144974/double-nanodomain-coupling-of-calcium-channels-ryanodine-receptors-and-bk-channels-controls-the-generation-of-burst-firing
#6
Tomohiko Irie, Laurence O Trussell
Action potentials clustered into high-frequency bursts play distinct roles in neural computations. However, little is known about ionic currents that control the duration and probability of these bursts. We found that, in cartwheel inhibitory interneurons of the dorsal cochlear nucleus, the likelihood of bursts and the interval between their spikelets were controlled by Ca(2+) acting across two nanodomains, one between plasma membrane P/Q Ca(2+) channels and endoplasmic reticulum (ER) ryanodine receptors and another between ryanodine receptors and large-conductance, voltage- and Ca(2+)-activated K(+) (BK) channels...
November 15, 2017: Neuron
https://www.readbyqxmd.com/read/29132927/whole-exome-sequencing-identified-a-pathogenic-mutation-in-ryr2-in-a-chinese-family-with-unexplained-sudden-death
#7
Yubi Lin, Siqi He, Zili Liao, Ruiling Feng, Ruilin Liu, Yongzheng Peng, Nan Yu, Hang Qi, Jia Chen, Zifeng Huang, Heping Lei, Yang Liu, Fang Rao, Chunyu Deng, Yumei Xue, Guolin Zhang, Bin Zhang, Hua Yao, Shulin Wu
OBJECTIVE: This study aimed to identify the pathogenic mutation in a Chinese family with unexplained sudden death (USD) or occasional syncope. MATERIALS AND METHODS: Whole exome sequencing and target capture sequencing were respectively conducted for two related patients. The genetic data was screened using the 1000 genomes project and SNP database (PubMed), and the identified mutations were assessed for predicted pathogenicity using the SIFT and Polyphen-2 algorithms...
October 10, 2017: Journal of Electrocardiology
https://www.readbyqxmd.com/read/29131945/enantioselectivity-of-2-2-3-5-6-pentachlorobiphenyl-pcb-95-atropisomers-toward-ryanodine-receptors-ryrs-and-their-influences-on-hippocampal-neuronal-networks
#8
Wei Feng, Jing Zheng, Gaelle Robin, Yao Dong, Makoto Ichikawa, Yoshihisa Inoue, Tadashi Mori, Takeshi Nakano, Isaac N Pessah
Nineteen ortho-substituted PCBs are chiral and found enantioselectively enriched in ecosystems. Their differential actions on biological targets are not understood. PCB 95 (2,2',3,5',6-pentachlorobiphenyl), a chiral PCB of current environmental relevance, is among the most potent towards modifying ryanodine receptors (RyR) function and Ca2+ signaling. PCB 95 atropisomers are separated and assigned aR- and aS-PCB 95 using 3 chiral-columns HPLC and circular dichroism spectroscopy. Studies of RyR1-enriched microsomes show aR-PCB 95 with >4X greater potency (EC50=0...
November 13, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29131158/ucp1-independent-signaling-involving-serca2b-mediated-calcium-cycling-regulates-beige-fat-thermogenesis-and-systemic-glucose-homeostasis
#9
Kenji Ikeda, Qianqian Kang, Takeshi Yoneshiro, Joao Paulo Camporez, Hiroko Maki, Mayu Homma, Kosaku Shinoda, Yong Chen, Xiaodan Lu, Pema Maretich, Kazuki Tajima, Kolapo M Ajuwon, Tomoyoshi Soga, Shingo Kajimura
Uncoupling protein 1 (UCP1) plays a central role in nonshivering thermogenesis in brown fat; however, its role in beige fat remains unclear. Here we report a robust UCP1-independent thermogenic mechanism in beige fat that involves enhanced ATP-dependent Ca(2+) cycling by sarco/endoplasmic reticulum Ca(2+)-ATPase 2b (SERCA2b) and ryanodine receptor 2 (RyR2). Inhibition of SERCA2b impairs UCP1-independent beige fat thermogenesis in humans and mice as well as in pigs, a species that lacks a functional UCP1 protein...
November 13, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29124635/atropisomers-of-2-2-3-3-6-6-hexachlorobiphenyl-pcb-136-exhibit-stereoselective-effects-on-activation-of-nuclear-receptors-in-vitro
#10
Kateřina Pěnčíková, Petra Brenerová, Lucie Svržková, Eva Hrubá, Lenka Pálková, Jan Vondráček, Hans-Joachim Lehmler, Miroslav Machala
PCB 136 is an environmentally relevant chiral PCB congener, which has been found in vivo to be present in form of rotational isomers (atropisomers). Its atropselective biotransformation or neurotoxic effects linked with sensitization of ryanodine receptor suggest that it might interact also with other intracellular receptors in a stereospecific manner. However, possible atropselective effects of PCB 136 on nuclear receptor transactivation remain unknown. Therefore, in this study, atropselective effects of PCB 136 on nuclear receptors controlling endocrine signaling and/or expression of xenobiotic and steroid hormone catabolism were investigated...
November 9, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29123133/aip-limits-neurotransmitter-release-by-inhibiting-calcium-bursts-from-the-ryanodine-receptor
#11
Bojun Chen, Ping Liu, Edward J Hujber, Yan Li, Erik M Jorgensen, Zhao-Wen Wang
Pituitary tumors are frequently associated with mutations in the AIP gene and are sometimes associated with hypersecretion of growth hormone. It is unclear whether other factors besides an enlarged pituitary contribute to the hypersecretion. In a genetic screen for suppressors of reduced neurotransmitter release, we identified a mutation in Caenorhabditis elegans AIPR-1 (AIP-related-1), which causes profound increases in evoked and spontaneous neurotransmitter release, a high frequency of spontaneous calcium transients in motor neurons and an enlarged readily releasable pool of vesicles...
November 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/29122978/the-structural-basis-of-ryanodine-receptor-ion-channel-function
#12
REVIEW
Gerhard Meissner
Large-conductance Ca(2+) release channels known as ryanodine receptors (RyRs) mediate the release of Ca(2+) from an intracellular membrane compartment, the endo/sarcoplasmic reticulum. There are three mammalian RyR isoforms: RyR1 is present in skeletal muscle; RyR2 is in heart muscle; and RyR3 is expressed at low levels in many tissues including brain, smooth muscle, and slow-twitch skeletal muscle. RyRs form large protein complexes comprising four 560-kD RyR subunits, four ∼12-kD FK506-binding proteins, and various accessory proteins including calmodulin, protein kinases, and protein phosphatases...
November 9, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29107248/molecular-cloning-mrna-expression-and-alternative-splicing-of-a-ryanodine-receptor-gene-from-the-citrus-whitefly-dialeurodes-citri-ashmead
#13
Guo-Rui Yuan, Ke-Yi Wang, Xing Mou, Ruo-Yu Luo, Wei Dou, Jin-Jun Wang
Insect ryanodine receptors are the main targets of diamide insecticides that have highly selective insecticidal activity but are less toxic to mammals. Therefore, these insecticides are ideal for pest control. Ryanodine receptors (RyRs) play a critical role in Ca(2+) signaling in muscle and non-muscle cells. In this study, we cloned the complete cDNA (DcRyR) of the RyR from the citrus whitefly, Dialeurodes citri, a serious pest of citrus orchards in China. The open reading frame of RyR is 15,378bp long and encodes a protein with 5126 amino acids with a computed molecular weight of 579...
October 2017: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/29107242/silence-of-inositol-1-4-5-trisphosphate-receptor-expression-decreases-cyantraniliprole-susceptibility-in-bemisia-tabaci
#14
Lei Guo, Pei Liang, Kuan Fang, Dong Chu
Cyantraniliprole is the second active ingredient of anthranilic diamide insecticide, and the first to control a cross-spectrum of chewing and sucking pests such as sweetpotato whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae). The inositol 1,4,5-trisphosphate receptor (IP3R) and ryanodine receptor (RyR) are two families of Ca(2+) release channels to raise the cytoplasmic free calcium concentration when it is activated by various extracellular stimuli. Previous study proved the over-expression of ryanodine receptor (RyR) was associated with the resistance to diamide insecticides, while the roles of IP3R in diamide resistance remain unknown...
October 2017: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/29101530/sudden-death-due-to-malignant-hyperthermia-with-a-mutation-of-ryr1-autopsy-morphology-and-genetic-analysis
#15
Wenhe Li, Lin Zhang, Yue Liang, Fang Tong, Yiwu Zhou
Malignant hyperthermia (MH) is an autosomal dominant disorder characterized by abnormal calcium homeostasis in skeletal muscles in response to triggering agents. Autopsy, morphology, and genetic analysis were performed on a 19-year-old man who died rapidly after exposure to sevoflurane during maxillofacial surgery. Muscle spasm around the operation area and limb rigidity occurred and renal tubules full of myoglobin casts were observed by microscopy. Ultrastructural changes in the skeletal muscles and the myocardium were detected by transmission electron microscopy (TEM)...
December 2017: Forensic Science, Medicine, and Pathology
https://www.readbyqxmd.com/read/29097735/mammalian-%C3%AE-2-ampk-regulates-intrinsic-heart-rate
#16
Arash Yavari, Mohamed Bellahcene, Annalisa Bucchi, Syevda Sirenko, Katalin Pinter, Neil Herring, Julia J Jung, Kirill V Tarasov, Emily J Sharpe, Markus Wolfien, Gabor Czibik, Violetta Steeples, Sahar Ghaffari, Chinh Nguyen, Alexander Stockenhuber, Joshua R St Clair, Christian Rimmbach, Yosuke Okamoto, Dongmei Yang, Mingyi Wang, Bruce D Ziman, Jack M Moen, Daniel R Riordon, Christopher Ramirez, Manuel Paina, Joonho Lee, Jing Zhang, Ismayil Ahmet, Michael G Matt, Yelena S Tarasova, Dilair Baban, Natasha Sahgal, Helen Lockstone, Rathi Puliyadi, Joseph de Bono, Owen M Siggs, John Gomes, Hannah Muskett, Mahon L Maguire, Youlia Beglov, Matthew Kelly, Pedro P N Dos Santos, Nicola J Bright, Angela Woods, Katja Gehmlich, Henrik Isackson, Gillian Douglas, David J P Ferguson, Jürgen E Schneider, Andrew Tinker, Olaf Wolkenhauer, Keith M Channon, Richard J Cornall, Eduardo B Sternick, David J Paterson, Charles S Redwood, David Carling, Catherine Proenza, Robert David, Mirko Baruscotti, Dario DiFrancesco, Edward G Lakatta, Hugh Watkins, Houman Ashrafian
AMPK is a conserved serine/threonine kinase whose activity maintains cellular energy homeostasis. Eukaryotic AMPK exists as αβγ complexes, whose regulatory γ subunit confers energy sensor function by binding adenine nucleotides. Humans bearing activating mutations in the γ2 subunit exhibit a phenotype including unexplained slowing of heart rate (bradycardia). Here, we show that γ2 AMPK activation downregulates fundamental sinoatrial cell pacemaker mechanisms to lower heart rate, including sarcolemmal hyperpolarization-activated current (I f) and ryanodine receptor-derived diastolic local subsarcolemmal Ca(2+) release...
November 2, 2017: Nature Communications
https://www.readbyqxmd.com/read/29097503/ryanodine-channel-complex-stabilizer-compound-s48168-arm210-as-a-disease-modifier-in-dystrophin-deficient-mdx-mice-proof-of-concept-study-and-independent-validation-of-efficacy
#17
Roberta Francesca Capogrosso, Paola Mantuano, Kitipong Uaesoontrachoon, Anna Cozzoli, Arcangela Giustino, Todd Dow, Sadish Srinivassane, Marina Filipovic, Christina Bell, Jack Vandermeulen, Ada Maria Massari, Michela De Bellis, Elena Conte, Sabata Pierno, Giulia Maria Camerino, Antonella Liantonio, Kanneboyina Nagaraju, Annamaria De Luca
Muscle fibers lacking dystrophin undergo a long-term alteration of Ca(2+) homeostasis, partially caused by a leaky Ca(2+) release ryanodine (RyR) channel. S48168/ARM210, an RyR calcium release channel stabilizer (a Rycal compound), is expected to enhance the rebinding of calstabin to the RyR channel complex and possibly alleviate the pathologic Ca(2+) leakage in dystrophin-deficient skeletal and cardiac muscle. This study systematically investigated the effect of S48168/ARM210 on the phenotype of mdx mice by means of a first proof-of-concept, short (4 wk), phase 1 treatment, followed by a 12 wk treatment (phase 2) performed in parallel by 2 independent laboratories...
November 2, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29078335/structural-insights-into-binding-of-stac-proteins-to-voltage-gated-calcium-channels
#18
Siobhan M Wong King Yuen, Marta Campiglio, Ching-Chieh Tung, Bernhard E Flucher, Filip Van Petegem
Excitation-contraction (EC) coupling in skeletal muscle requires functional and mechanical coupling between L-type voltage-gated calcium channels (CaV1.1) and the ryanodine receptor (RyR1). Recently, STAC3 was identified as an essential protein for EC coupling and is part of a group of three proteins that can bind and modulate L-type voltage-gated calcium channels. Here, we report crystal structures of tandem-SH3 domains of different STAC isoforms up to 1.2-Å resolution. These form a rigid interaction through a conserved interdomain interface...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29071820/application-of-multigene-panel-sequencing-in-patients-with-prolonged-rate-corrected-qt-interval-and-no-pathogenic-variants-detected-in-kcnq1-kcnh2-and-scn5a
#19
Soo Hyun Seo, So Yeon Kim, Sung Im Cho, Hyunwoong Park, Seungjun Lee, Jong Moon Choi, Man Jin Kim, Jee Soo Lee, Kyung Jin Ahn, Mi Kyoung Song, Eun Jung Bae, Sung Sup Park, Moon Woo Seong
Long QT syndrome (LQTS) is an inherited cardiac disease characterized by a prolonged heart rate-corrected QT (QTc) interval. We investigated the genetic causes in patients with prolonged QTc intervals who were negative for pathogenic variants in three major LQTS-related genes (KCNQ1, KCNH2, and SCN5A). Molecular genetic testing was performed using a panel including 13 LQTS-related genes and 67 additional genes implicated in other cardiac diseases. Overall, putative genetic causes of prolonged QTc interval were identified in three of the 30 patients (10%)...
January 2018: Annals of Laboratory Medicine
https://www.readbyqxmd.com/read/29062463/antioxidant-treatment-reduces-formation-of-structural-cores-and-improves-muscle-function-in-ryr1-y522s-wt-mice
#20
Antonio Michelucci, Alessandro De Marco, Flavia A Guarnier, Feliciano Protasi, Simona Boncompagni
Central core disease (CCD) is a congenital myopathy linked to mutations in the ryanodine receptor type 1 (RYR1), the sarcoplasmic reticulum Ca(2+) release channel of skeletal muscle. CCD is characterized by formation of amorphous cores within muscle fibers, lacking mitochondrial activity. In skeletal muscle of RYR1(Y522S/WT) knock-in mice, carrying a human mutation in RYR1 linked to malignant hyperthermia (MH) with cores, oxidative stress is elevated and fibers present severe mitochondrial damage and cores...
2017: Oxidative Medicine and Cellular Longevity
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