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Sarcoplasmic reticulum

Chu Shan Tan, Mun Fei Yam
Previous studies have demonstrated that 3'-hydroxy-5,6,7,4'-tetramethoxyflavone (TMF) content in Orthosiphon stamineus fractions correlate with its vasorelaxation activity. Even with the availability of previous studies, there is still very little information on the vasorelaxation effect of TMF, and few scientific studies have been carried out. Therefore, the present study was designed to investigate the vasorelaxation activity and mechanism of action of the TMF. The vasorelaxation activity and the underlying mechanisms of TMF were evaluated on thoracic aortic rings isolated from Sprague Dawley rats...
March 19, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
Connor M Pettem, Jennifer M Briens, David M Janz, Lynn P Weber
Selenium (Se) is considered an essential trace element, involved in important physiological and metabolic functions for all vertebrate species. Fish require dietary concentrations of 0.1-0.5 μg Se/g dry mass (d.m.) to maintain normal physiological and selenoprotein function, however concentrations exceeding 3 μg/g d.m. have been shown to cause toxicity. As Se is reported to have a narrow margin between essentiality and toxicity, there is growing concern surrounding the adverse effects of elevated Se exposure caused by anthropogenic activities...
March 8, 2018: Aquatic Toxicology
Alexey E Lyashkov, Joachim Beahr, Edward G Lakatta, Yael Yaniv, Victor A Maltsev
Recent data suggest that cardiac pacemaker cell function is determined by numerous time-, voltage-, and Ca-dependent interactions of cell membrane electrogenic proteins (M-clock) and intracellular Ca cycling proteins (Ca-clock), forming a coupled-clock system. Many aspects of the coupled-clock system, however, remain underexplored. The key players of the system are Ca release channels (ryanodine receptors), generating local Ca releases (LCRs) from sarcoplasmic reticulum, electrogenic Na/Ca exchanger (NCX) current, and L-type Ca current (ICaL )...
March 13, 2018: Biophysical Journal
L V Tat'yanenko, N A Sanina, O V Dobrokhotova, A I Kotelnikov, N S Goryachev, I I Pihteleva, G I Kozub, T A Kondrateva
The effect of iron nitrosyl complexes, NO donors, of a general formula [Fe2 (L)2 (NO)4 ] with functional sulfur-containing ligands (L-3-nitro-phenol-2-yl, 4-nitro-phenol-2-yl, or 1-methyl-tetrazol-5-yl) on the activity of sarcoplasmic reticulum Ca2+ -ATPase and cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) was studied. The test complexes uncoupled the hydrolytic and transport functions of Ca2+ - ATPase, thus disturbing the balance of Ca2+ ions in cells, which may affect the formation of thrombi and adhesion of metastatic cells to the endothelium of capillaries...
January 2018: Doklady. Biochemistry and Biophysics
Jill K Badin, Ayeeshik Kole, Benjamin Stivers, Victor Progar, Anisha Pareddy, Mouhamad Alloosh, Michael Sturek
BACKGROUND: There is a preponderance of evidence implicating diabetes with increased coronary artery disease (CAD) and calcification (CAC) in human patients with metabolic syndrome (MetS), but the effect of diabetes on CAD severity in animal models remains controversial. We investigated whether diabetes exacerbates CAD/CAC and intracellular free calcium ([Ca2+ ]i ) dysregulation in the clinically relevant Ossabaw miniature swine model of MetS. METHODS: Sixteen swine, eight with alloxan-induced diabetes, were fed a hypercaloric, atherogenic diet for 6 months...
March 9, 2018: Journal of Translational Medicine
Tian Li, Yafeng Shen, Li Su, Xiaoyan Fan, Fangxing Lin, Xuting Ye, Dianer Ding, Ying Tang, Yang Yongji, Changhai Lei, Shi Hu
Post-ischemic heart failure is a major cause of death worldwide. Reperfusion of infarcted heart tissue after myocardial infarction has been an important medical intervention to improve outcomes. However, disturbances in Ca2+ and redox homeostasis at the cellular level caused by ischemia/reperfusion remain major clinical challenges. In this study, we investigated the potential of adeno-associated virus (AAV)-9-mediated cardiac expression of a Type-2 ryanodine receptor (RyR2) degradation-associated gene, Presenilin 1 (PSEN1), to combat post-ischemic heart failure...
March 9, 2018: Journal of Drug Targeting
Michela Pecoraro, Michele Ciccarelli, Antonella Fiordelisi, Guido Iaccarino, Aldo Pinto, Ada Popolo
Doxorubicin (DOXO) administration induces alterations in Connexin 43 (Cx43) expression and localization, thus, inducing alterations in chemical and electrical signal transmission between cardiomyocytes and in intracellular calcium homeostasis even evident after a single administration. This study was designed to evaluate if Diazoxide (DZX), a specific opener of mitochondrial KATP channels widely used for its cardioprotective effects, can fight DOXO-induced cardiotoxicity in a short-time mouse model. DZX (20 mg/kg i...
March 7, 2018: International Journal of Molecular Sciences
Alfredo Criollo, Francisco Altamirano, Zully Pedrozo, Gabriele G Schiattarella, Dan L Li, Pablo Rivera-Mejías, Cristian Sotomayor-Flores, Valentina Parra, Elisa Villalobos, Pavan K Battiprolu, Nan Jiang, Herman I May, Eugenia Morselli, Stefan Somlo, Humberto de Smedt, Thomas G Gillette, Sergio Lavandero, Joseph A Hill
AIMS: Considerable evidence points to critical roles of intracellular Ca2+ homeostasis in the modulation and control of autophagic activity. Yet, underlying molecular mechanisms remain unknown. Mutations in the gene (pkd2) encoding polycystin-2 (PC2) are associated with autosomal dominant polycystic kidney disease (ADPKD), the most common inherited nephropathy. PC2 has been associated with impaired Ca2+ handling in cardiomyocytes and indirect evidence suggests that this protein may be involved in autophagic control...
March 5, 2018: Journal of Molecular and Cellular Cardiology
Xudong Chen, Yundi Feng, Yunlong Huo, Wenchang Tan
Ca2+ sparks and Ca2+ quarks, arising from clustered and rogue ryanodine receptors (RyRs), are significant Ca2+ release events from the junctional sarcoplasmic reticulum (JSR). Based on the anomalous subdiffusion of Ca2+ in the cytoplasm, a mathematical model was developed to investigate the effects of rogue RyRs on Ca2+ sparks in cardiac myocytes. Ca2+ quarks and sparks from the stochastic opening of rogue and clustered RyRs are numerically reproduced and agree with experimental measurements. It is found that the stochastic opening Ca2+ release units (CRUs) of clustered RyRs are regulated by free Ca2+ concentration in the JSR lumen (i...
February 2018: Royal Society Open Science
Eduardo Ríos
Ryanodine-sensitive intracellular Ca2+ channels (RyRs) open upon binding Ca2+ at cytosolic-facing sites. This results in concerted, self-reinforcing opening of RyRs clustered in specialized regions on the membranes of Ca2+ storage organelles (endoplasmic reticulum and sarcoplasmic reticulum), a process that produces Ca2+ -induced Ca2+ release (CICR). The process is optimized to achieve large but brief and localized increases in cytosolic Ca2+ concentration, a feature now believed to be critical for encoding the multiplicity of signals conveyed by this ion...
March 7, 2018: Journal of General Physiology
Wajihah Mughal, Matthew Martens, Jared Field, Donald Chapman, Jianhe Huang, Sunil Rattan, Yan Hai, Kyle G Cheung, Stephanie Kereliuk, Adrian R West, Laura K Cole, Grant M Hatch, William Diehl-Jones, Richard Keijzer, Vernon W Dolinsky, Ian M Dixon, Michael S Parmacek, Joseph W Gordon
Myocardin is a transcriptional co-activator required for cardiovascular development, but also promotes cardiomyocyte survival through an unclear molecular mechanism. Mitochondrial permeability transition is implicated in necrosis, while pore closure is required for mitochondrial maturation during cardiac development. We show that loss of myocardin function leads to subendocardial necrosis at E9.5, concurrent with elevated expression of the death gene Nix. Mechanistically, we demonstrate that myocardin knockdown reduces microRNA-133a levels to allow Nix accumulation, leading to mitochondrial permeability transition, reduced mitochondrial respiration, and necrosis...
March 6, 2018: Cell Death and Differentiation
Sarah E D Nelson, Kim N Ha, Tata Gopinath, Mara H Exline, Alessandro Mascioni, David D Thomas, Gianluigi Veglia
Approximately, 70% of the Ca2+ ion transport into the sarcoplasmic reticulum is catalyzed by the sarcoplasmic reticulum Ca2+ -ATPase (SERCA), whose activity is endogenously regulated by phospholamban (PLN). PLN comprises a TM inhibitory region and a cytoplasmic regulatory region that harbors a consensus sequence for cAMP-dependent protein kinase (PKA). The inhibitory region binds the ATPase, reducing its apparent Ca2+ binding affinity. β-adrenergic stimulation activates PKA, which phosphorylates PLN at Ser 16, reversing its inhibitory function...
March 1, 2018: Biochimica et Biophysica Acta
Elisa Bovo, Stefan R Mazurek, Aleksey V Zima
Defective Ca2+ regulation plays a key role in the blunted force-frequency response in heart failure (HF). Since HF is commonly associated with oxidative stress, we studied whether oxidation of ryanodine receptor (RyR2) contributes to this defect. In control ventricular myocytes, oxidative stress induced formation of disulfide bonds between RyR2 subunits: intersubunit cross-linking (XL). Western blot analysis and Ca2+ imaging revealed a strong positive correlation between RyR2 XL and sarcoplasmic reticulum (SR) Ca2+ leak...
March 2, 2018: Pflügers Archiv: European Journal of Physiology
Yan G Zhao, Hong Zhang
The ER forms contacts with other endomembrane systems to exchange materials (e.g., calcium and lipids) and also to modulate dynamic organelle processes, including fission, cargo sorting and movement. During autophagosome formation, dynamic contacts between the ER and the phagophore membrane are crucial for phagophore expansion and closure. Little is known about the mechanisms underlying the formation and disassembly of the ER contacts. We found that the ER-localized autophagy protein EPG-3/VMP1 plays an essential role in controlling ER-phagophore dissociation and also the disassembly of ER contacts with LDs, mitochondria and endolysosomes...
March 1, 2018: Autophagy
Yuting Zhai, Yuanyuan Luo, Pei Wu, Dongye Li
Sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a) is a target of interest in gene therapy for heart failure with reduced ejection fraction (HFrEF). However, the results of an important clinical study, the Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) trial, were controversial. Promising results were observed in the CUPID 1 trial, but the results of the CUPID 2 trial were negative. The factors that caused the controversial results remain unclear. Importantly, enrolled patients were required to have a higher plasma level of B-type natriuretic peptide (BNP) in the CUPID 2 trial...
February 24, 2018: Journal of Medical Genetics
Jing Xiong, Xijun Liu, Yunyun Gong, Peng Zhang, Sujing Qiang, Qian Zhao, Rong Guo, Yunyun Qian, Lipeng Wang, Li Zhu, Ruiwu Wang, Zhiyuan Hao, Han Wen, Jingying Zhang, Kai Tang, Wang-Fu Zang, Zhiguang Yuchi, Haijun Chen, S R Wayne Chen, Wenjun Zheng, Shi-Qiang Wang, Ya-Wei Xu, Zheng Liu
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a condition that is characterized by an abnormal heart rhythm in response to physical or emotional stress. The majority CPVT patients carry mutations in the RYR2 gene that encodes the calcium release channel/ryanodine receptor (RyR2) in cardiomyocytes. The pathogenic mechanisms that account for the clinical phenotypes of CPVT are still elusive. We have identified a de novo mutation, A165D, from a CPVT patient. We found that CPVT phenotypes are recapitulated in A165D knock-in mice...
February 22, 2018: Journal of Molecular and Cellular Cardiology
Ying Zhang, Lei Jiao, Li-Hua Sun, Yanru Li, Yuqiu Gao, Chaoqian Xu, Yingchun Shao, Mengmeng Li, Chunyan Li, Yanjie Lu, Zhenwei Pan, Li-Na Xuan, Yiyuan Zhang, Qingqi Li, Rui Yang, Yuting Zhuang, Yong Zhang, Baofeng Yang
<u>Rationale:</u> Ca2+ homeostasis, a critical determinant of cardiac contractile function, is critically regulated by sarcoplasmic reticulum Ca2+ -ATPase 2a (SERCA2a). Our previous study has identified ZFAS1 as a new long non-coding RNA (lncRNA) biomarker of acute myocardial infarction (MI). <u>Objective:</u> To evaluate the effects of ZFAS1 on SERCA2a and the associated Ca2+ homeostasis and cardiac contractile function in the setting of MI. <u>Methods and Results:</u> ZFAS1 expression was robustly increased in cytoplasm and sarcoplasmic reticulum in a mouse model of MI and a cellular model of hypoxia...
February 23, 2018: Circulation Research
Alexander Polster, Benjamin R Nelson, Symeon Papadopoulos, Eric N Olson, Kurt G Beam
In skeletal muscle, residues 720-764/5 within the CaV 1.1 II-III loop form a critical domain that plays an essential role in transmitting the excitation-contraction (EC) coupling Ca2+ release signal to the type 1 ryanodine receptor (RyR1) in the sarcoplasmic reticulum. However, the identities of proteins that interact with the loop and its critical domain and the mechanism by which the II-III loop regulates RyR1 gating remain unknown. Recent work has shown that EC coupling in skeletal muscle of fish and mice depends on the presence of Stac3, an adaptor protein that is highly expressed only in skeletal muscle...
February 21, 2018: Journal of General Physiology
Gaetano Santulli, Daniel Lewis, Amedee des Georges, Andrew R Marks, Joachim Frank
Ryanodine receptors (RyRs) are ubiquitous intracellular calcium (Ca2+ ) release channels required for the function of many organs including heart and skeletal muscle, synaptic transmission in the brain, pancreatic beta cell function, and vascular tone. In disease, defective function of RyRs due either to stress (hyperadrenergic and/or oxidative overload) or genetic mutations can render the channels leaky to Ca2+ and promote defective disease-causing signals as observed in heat failure, muscular dystrophy, diabetes mellitus, and neurodegerative disease...
2018: Sub-cellular Biochemistry
Joseph O Primeau, Gareth P Armanious, M'Lynn E Fisher, Howard S Young
The calcium pump (a.k.a. Ca2+ -ATPase or SERCA) is a membrane transport protein ubiquitously found in the endoplasmic reticulum (ER) of all eukaryotic cells. As a calcium transporter, SERCA maintains the low cytosolic calcium level that enables a vast array of signaling pathways and physiological processes (e.g. synaptic transmission, muscle contraction, fertilization). In muscle cells, SERCA promotes relaxation by pumping calcium ions from the cytosol into the lumen of the sarcoplasmic reticulum (SR), the main storage compartment for intracellular calcium...
2018: Sub-cellular Biochemistry
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