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Ryanodine

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https://www.readbyqxmd.com/read/29678654/4tm-trpm8-channels-are-new-gatekeepers-of-the-er-mitochondria-ca-2-transfer
#1
Gabriel Bidaux, Dmitri Gordienko, George Shapovalov, Valerio Farfariello, Anne-Sophie Borowiec, Oksana Iamshanova, Loic Lemonnier, Maxime Gueguinou, Roseline Guibon, Gaelle Fromont, Mélanie Paillard, Yves Gouriou, Christophe Chouabe, Etienne Dewailly, Dimitra Gkika, Pilar López-Alvarado, J Carlos Menéndez, Laurent Héliot, Christian Slomianny, Natalia Prevarskaya
Calcium (Ca2+ ) release from the endoplasmic reticulum plays an important role in many cell-fate defining cellular processes. Traditionally, this Ca2+ release was associated with the ER Ca2+ release channels, inositol 1,4,5‑triphosphate receptor (IP3 R) and ryanodine receptor (RyR). Lately, however, other calcium conductances have been found to be intracellularly localized and to participate in cell fate regulation. Nonetheless, molecular identity and functional properties of the ER Ca2+ release mechanisms associated with multiple diseases, e...
April 17, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29676187/decrease-of-ryr2-in-the-prion-infected-cell-line-and-in-the-brains-of-the-scrapie-infected-mice-models-and-the-patients-of-human-prion-diseases
#2
Qi Shi, Jian-Le Li, Yue Ma, Li-Ping Gao, Kang Xiao, Jing Wang, Wei Zhou, Cao Chen, Yan-Jun Guo, Xiao-Ping Dong
The levels of ryanodine receptors (RyRs) are usually increased in the brains of human Alzheimer disease (AD) and AD animal models. To evaluate the underlying alteration of brain RyRs in prion disease, scrapie infected cell line SMB-S15 and its infected mice were tested. RyR2 specific Western blots revealed markedly decreased RyR2 levels both in the cells and in the brains of infected mice. Assays of the brain samples of other scrapie (agents 139A and ME7) infected mice collected at different time-points during incubation period showed time-dependent decreases of RyR2...
April 20, 2018: Prion
https://www.readbyqxmd.com/read/29674523/efficient-high-throughput-screening-by-er-ca-2-measurement-to-identify-inhibitors-of-ryanodine-receptor-ca2-release-channels
#3
Takashi Murayama, Nagomi Kurebayashi, Mari Ikegami-Yuasa, Shuichi Mori, Yukina Suzuki, Ryunosuke Akima, Haruo Ogawa, Junji Suzuki, Kazunori Kanemaru, Hideto Oyamada, Yuji Kiuchi, Masamitsu Iino, Hiroyuki Kagechika, Takashi Sakurai
Genetic mutations in ryanodine receptors (RyRs), Ca2+-release channels in the sarcoplasmic reticulum essential for muscle contractions, cause various skeletal muscle and cardiac diseases. Because the main underlying mechanism of the pathogenesis is overactive Ca2+ release by gain-of-function of the RyR channel, inhibition of RyRs is expected to be a promising treatment for these diseases. Here, to identify inhibitors specific to skeletal muscle type 1 RyR (RyR1), we developed a novel high-throughput screening (HTS) platform using time-lapse fluorescence measurement of Ca2+ concentrations in the endoplasmic reticulum (ER) ([Ca2+]ER)...
April 19, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29668881/hyperactive-ryanodine-receptors-in-human-heart-failure-and-ischemic-cardiomyopathy-reside-outside-of-couplons
#4
Eef Dries, Demetrio J Santiago, Guillaume Gilbert, Ilse Lenaerts, Bert Vandenberk, Chandan K Nagaraju, Daniel M Johnson, Patricia Holemans, H Llewelyn Roderick, Niall Macquaide, Piet Claus, Karin R Sipido
Aims: In ventricular myocytes from humans and large mammals, the transverse and axial tubular system (TATS) network is less extensive than in rodents with consequently a greater proportion of ryanodine receptors (RyRs) not coupled to this membrane system. TATS remodeling in heart failure (HF) and after myocardial infarction (MI) increases the fraction of non-coupled RyR. Here we investigate whether this remodeling alters the activity of coupled and non-coupled RyR sub-populations through changes in local signaling...
April 14, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29668377/pulsed-infrared-releases-ca-2-from-the-endoplasmic-reticulum-of-cultured-spiral-ganglion-neurons
#5
John N Barrett, Samantha Rincon, Jayanti Singh, Cristina Matthewman, Julio Pasos, Ellen F Barrett, Suhrud M Rajguru
We investigated the effects of pulsed infrared radiation (IR, 1863 nm) stimulation on cytosolic [Ca2+ ] in inner ear spiral ganglion neurons cultured from day 4 postnatal mice and loaded with a fluorescent Ca2+ indicator (fluo-4, -5F or -5N). IR pulse trains (200 µs, 200-250 Hz, 2-5 s) delivered via an optical fiber coupled to IR source produced a rapid, transient temperature increase of 6-11ºC (above a baseline of 24-30 ºC) and evoked transient increases in both nuclear and cytosolic [Ca2+ ] of 0.20 - 1...
April 18, 2018: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29660904/ryanodine-receptor-antagonism-alleviates-skeletal-muscle-ischemia-reperfusion-injury-by-modulating-tnf-%C3%AE-and-il-10
#6
Hai-Peng Lin, Yan-Qing Zheng, Zhi-Ping Zhou, Gao-Xiong Wang, Ping-Fan Guo
BACKGROUND: Intracellular calcium overload has been implicated in various pathological conditions including ischemia reperfusion injury. This study aims to explore the effect and probable mechanism of dantrolene, a ryanodine receptor and intracellular calcium antagonist, on the skeletal muscle ischemia reperfusion injury. MATERIALS AND METHODS: SD rats were randomly divided into three groups: sham group which underwent anaesthesia and exposure of femoral vein, reperfusion group that received 2 h ischemia and the amount of diluent via femoral vein before 4 h reperfusion, dantrolene group that underwent 2 h ischemia and was given 2 mg/kg dantrolene via femoral vein before 4 h reperfusion...
April 13, 2018: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/29627324/from-excitation-to-intracellular-ca-2-movements-in-skeletal-muscle-basic-aspects-and-related-clinical-disorders
#7
REVIEW
Bruno Allard
In skeletal muscle fiber, excitation-contraction coupling corresponds to the sequence of events occurring from action potential firing to initiation of contraction by an increase in cytosolic Ca2+ . These events are elicited in response to excitation of the motor neuron which induces trains of action potentials in the muscle cell that spread along the sarcolemma and in depth along the T-tubule membrane. Depolarization of the T-tubule membrane induces a conformational change in a protein complex, called the dihydropyridine receptor, which opens a calcium channel anchored in the membrane of the sarcoplasmic reticulum, called the ryanodine receptor, in charge of release of Ca2+ ions that activate contractile proteins...
March 9, 2018: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/29626986/molecular-characterization-and-expression-profiling-of-ryanodine-receptor-gene-in-the-pink-stem-borer-sesamia-inferens-walker
#8
Shun-Fan Wu, Dan-Dan Zhao, Jing-Mei Huang, Si-Qi Zhao, Li-Qi Zhou, Cong-Fen Gao
The susceptibilities of three field populations of pink stem borer (PSB), Sesamia inferens (walker) to diamide insecticides, chlorantraniliprole and flubendiamide, were evaluated in this study. The results showed that these PSB field populations were still sensitive to the two diamide insecticides after many years of exposure. To further understand PSB and diamide insecticide, the full-length ryanodine receptor (RyR) cDNA (named as SiRyR), the molecular target of diamide insecticides was cloned from PSB and characterized...
April 2018: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/29617551/organohalogens-naturally-biosynthesized-in-marine-environments-and-produced-as-disinfection-by-products-alter-sarco-endoplasmic-reticulum-ca-2-dynamics
#9
Jing Zheng, Shaun M K Mckinnie, Abrahim El Gamal, Wei Feng, Yao Dong, Vinayak Agarwal, William Fenical, Abdhesh Kumar, Zhengyu Cao, Bradley S Moore, Isaac N Pessah
Contemporary sources of organohalogens produced as disinfection by-products (DBPs) are receiving considerable attention as emerging pollutants because of their abundance, persistence, and potential to structurally mimic natural organohalogens produced by bacteria that serve signaling and/or toxicological functions in marine environments. Here we tested 34 organohalogens from anthropogenic and marine sources to identify compounds active towards ryanodine receptor (RyR1), known toxicological targets of non-dioxin-like polychlorinated biphenyls (PCBs) and polybrominated diphenylethers (PBDEs)...
April 4, 2018: Environmental Science & Technology
https://www.readbyqxmd.com/read/29610596/catecholaminergic-polymorphic-ventricular-tachycardia-looking-to-the-future
#10
Andreea Elena Velcea, Calin Siliste, Dragos Vinereanu
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inheritable cardiac disorder, characterized by polymorphic ventricular tachycardia (PVT) or bidirectional ventricular tachycardia, triggered by adrenergic stress, and manifested most frequently as syncope or sudden cardiac death. The disease has a heterogeneous genetic basis, with mutations in the genes encoding the ryanodine and calsequestrin channels accounting for the majority of cases. The diagnosis of CPVT is established in individuals with polymorphic ventricular premature beats, PVT or bidirectional ventricular tachycardia documented during exercise or adrenergic stress, who have a structurally normal heart and normal resting ECG...
December 2017: Mædica
https://www.readbyqxmd.com/read/29600763/ryanodine-receptors-for-drugs-and-insecticides-an-overview
#11
Hui Xu, Zhiqiang Sun
Ryanodine receptors (RyRs) are calcium channels located on the endo(sarco)plasmic reticulum of muscle cells and neurons. They regulate release of stored intracellular calcium and play a critical role in muscle contraction. The N-terminal part of these receptors accounts for roughly 80% and contains the binding sites for diverse RyRs modulators. The C-terminal domain contains the transmembrane region. Ryanodine, a plant alkaloid, has been investigated extensively as a potential pest control agent but no selectivity between mammalians and insect pests...
March 29, 2018: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/29595193/xyloketal-b-exerts-antihypertensive-effect-in-renovascular-hypertensive-rats-via-the-no-sgc-cgmp-pathway-and-calcium-signaling
#12
Li-Yan Zhao, Jie Li, Xiong-Qing Huang, Guo-Hao Wang, Xiao-Fei Lv, Wei-Feng Meng, Wen-Liang Chen, Ji-Yan Pang, Yong-Cheng Lin, Hong-Shuo Sun, Guan-Lei Wang, Yao-Min Du
Xyloketal B (Xyl-B) is a novel marine compound isolated from mangrove fungus Xylaria sp. (No 2508). We previously showed that Xyl-B promoted endothelial NO release and protected against atherosclerosis through the Akt/eNOS pathway. Vascular NO production regulates vasoconstriction in central and peripheral arteries and plays an important role in blood pressure control. In this study, we examined whether Xyl-B exerted an antihypertensive effect in a hypertensive rat model, and further explored the possible mechanisms underlying its antihypertensive action...
March 29, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29593014/ryanodine-receptor-calcium-leak-in-circulating-b-lymphocytes-as-a-biomarker-in-heart-failure
#13
Alexander Kushnir, Gaetano Santulli, Steven R Reiken, Ellie Coromilas, Sarah J Godfrey, Danielle L Brunjes, Paolo C Colombo, Melana Yuzefpolskaya, Seth I Sokol, Richard N Kitsis, Andrew R Marks
Background -Advances in congestive heart failure (CHF) management depend on biomarkers for monitoring disease progression and therapeutic response. During systole, intracellular Ca2+ is released from the sarcoplasmic reticulum (SR) into the cytoplasm through type 2 ryanodine receptor/Ca2+ release channels (RyR2). In CHF, chronically elevated circulating catecholamine levels cause pathologic remodeling of RyR2 resulting in diastolic SR Ca2+ leak, and decreased myocardial contractility. Similarly, skeletal muscle contraction requires SR Ca2+ release through type-1 ryanodine receptors (RyR1), and chronically elevated catecholamine levels in CHF cause RyR1 mediated SR Ca2+ leak, contributing to myopathy and weakness...
March 28, 2018: Circulation
https://www.readbyqxmd.com/read/29590321/polymorphisms-within-ryr3-gene-are-associated-with-risk-and-age-at-onset-of-hypertension-diabetes-and-alzheimer-s-disease
#14
Shaoqing Gong, Brenda Bin Su, Hugo Tovar, ChunXiang Mao, Valeria Gonzalez, Ying Liu, Yongke Lu, Ke-Sheng Wang, Chun Xu
Background: Hypertension affects 33% of Americans while type 2 diabetes and Alzheimer's disease (AD) affect 10% of Americans, respectively. Ryanodine receptor 3 gene (RYR3) codes for the ryanodine receptor which functions to release stored endoplasmic reticulum calcium ions (Ca2+ ) to increase intracellular Ca2+ concentration. Increasing studies demonstrate that altered levels of intracellular Ca2+ affects cardiac contraction, insulin secretion and neurodegeneration. In this study, we investigated associations of the RYR3 genetic variants with hypertension, AD, and diabetes...
March 26, 2018: American Journal of Hypertension
https://www.readbyqxmd.com/read/29588343/ionotropic-and-metabotropic-mechanisms-of-allosteric-modulation-of-%C3%AE-7-nicotinic-receptor-intracellular-calcium
#15
Justin R King, Aman Ullah, Ellen Bak, Saleet Jafri, Nadine Kabbani
The pharmacological targeting of the α7 nicotinic acetylcholine receptor (α7) is a promising strategy in the development of new drugs for neurological diseases Because α7 receptors regulate cellular calcium, we investigated how the prototypical type II positive allosteric modulator PNU120596 affects α7 mediated calcium signaling. Live imaging experiments show that PNU120596 augments ryanodine receptor driven calcium-induced calcium release (CICR), IP3 induced calcium release (IICR), and PLC activation by the α7 receptor...
March 27, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29576847/differentiation-of-promonocytic-u937-cells-to-monocytes-is-associated-with-reduced-mitochondrial-transport-of-ascorbic-acid
#16
Maddalena Scotti, Mara Fiorani, Andrea Guidarelli, Orazio Cantoni
Growth of promonocytic U937 cells in the presence of DMSO promotes their differentiation to monocytes. After 4 days of culture in differentiating medium, these cells ceased to proliferate, displayed downregulated ryanodine receptor expression, and responded to specific stimuli with enhanced NADPH-oxidase-derived superoxide formation or cytosolic phospholipase A2 -dependent arachidonic acid release. We found that the 4-day differentiation process is also associated with downregulated SVCT2 mRNA expression, in the absence of apparent changes in SVCT2 protein expression and transport rate of ascorbic acid (AA)...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29576327/parental-mosaicism-in-ryr1-related-central-core-disease
#17
S Marks, E van Ruitenbeek, P Fallon, P Johns, R Phadke, R Mein, S Mohammed, H Jungbluth
Myopathies due to mutations in the skeletal muscle ryanodine receptor (RYR1) gene are amongst the most common non-dystrophic neuromuscular disorders and have been associated with both dominant and recessive inheritance. Several cases with apparently de novo dominant inheritance have been reported. Here we report two siblings with features of Central Core Disease (CCD) born to unaffected parents. Genetic testing revealed a heterozygous dominant RYR1 c.14582G>A (p. Arg4861His) mutation previously identified in other CCD pedigrees...
February 26, 2018: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/29574066/impaired-ca-2-handling-in-resistance-arteries-from-genetically-obese-zucker-rats-role-of-the-pi3k-erk1-2-and-pkc-signaling-pathways
#18
Ana Sánchez, Cristina Contreras, Belén Climent, Alejandro Gutiérrez, Mercedes Muñoz, Albino García-Sacristán, Miguel López, Luis Rivera, Dolores Prieto
The impact of obesity on vascular smooth muscle (VSM) Ca2+ handling and vasoconstriction, and its regulation by the phosphatidylinositol 3-kinase (PI3K), mitogen activated protein kinase (MAPK) and protein kinase C (PKC) were assessed in mesenteric arteries (MA) from obese Zucker rats (OZR). Simultaneous measurements of intracellular Ca2+ ([Ca2+ ]i ) and tension were performed in MA from OZR and compared to lean Zucker rats (LZR), and the effects of selective inhibitors of PI3K, ERK-MAPK kinase and PKC were assessed on the functional responses of VSM voltage-dependent L-type Ca2+ channels (CaV 1...
March 21, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29565713/sunlight-incidence-vitamin-d-deficiency-and-alzheimer-s-disease
#19
Alice Barros Câmara, Iara Dantas de Souza, Rodrigo Juliani Siqueira Dalmolin
Vitamin D (VD) deficiency is a growing problem, affecting a significant portion of the population in many countries. VD deficiency may be related to several diseases, including Alzheimer's disease (AD). This study aimed to review the relationship between VD deficiency and AD. We describe the proteins involved in AD pathogenesis and how those proteins can be influenced by VD deficiency. We also investigated a relationship between AD death rate and solar radiation and we found an increased AD death rate in countries with low sunlight...
March 22, 2018: Journal of Medicinal Food
https://www.readbyqxmd.com/read/29563152/adrenaline-stimulates-glucagon-secretion-by-tpc2-dependent-ca-2-mobilization-from-acidic-stores-in-pancreatic-%C3%AE-cells
#20
Alexander Hamilton, Quan Zhang, Albert Salehi, Mara Willems, Jakob G Knudsen, Anna K Ringgaard, Caroline E Chapman, Alejandro Gonzalez-Alvarez, Nicoletta C Surdo, Manuela Zaccolo, Davide Basco, Paul R V Johnson, Reshma Ramracheya, Guy A Rutter, Antony Galione, Patrik Rorsman, Andrei I Tarasov
Adrenaline is a powerful stimulus of glucagon secretion. It acts by activation of β-adrenergic receptors but the downstream mechanisms have only been partially elucidated. Here we have examined the effects of adrenaline in mouse and human α-cells by a combination of electrophysiology, imaging of Ca2+ and PKA activity and hormone release measurements. We found that stimulation of glucagon secretion correlated with a PKA- and EPAC2-dependent (inhibited by PKI and ESI-05, respectively) elevation of [Ca2+ ]i in α-cells, which occurred without stimulation of electrical activity, persisted in the absence of extracellular Ca2+ but was sensitive to ryanodine, bafilomycin and thapsigargin...
March 21, 2018: Diabetes
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