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https://www.readbyqxmd.com/read/29162778/ryanodine-receptor-type-2-plays-a-role-in-the-development-of-cardiac-fibrosis-under-mechanical-stretch-through-tgf%C3%AE-1
#1
Zhiwen Ding, Jie Yuan, Yanyan Liang, Jian Wu, Hui Gong, Yong Ye, Guoliang Jiang, Peipei Yin, Yang Li, Guoping Zhang, Chunjie Yang, Junjie Guo, Zhidan Chen, Xingxu Wang, Liqing Weng, Yunzeng Zou
Ryanodine receptor type 2 (RyR-2), the main Ca(2+) release channel from sarcoplasmic reticulum in cardiomyocytes, plays a vital role in the regulation ofmyocardial contractile function and cardiac hypertrophy. However, the role of RyR-2 in cardiac fibrosis during the development of cardiac hypertrophy remains unclear.In this study, we examined whether RyR-2 regulates TGFβ1, which is secreted from cardiomyocytes and exerts on cardiac fibrosis using cultured cardiomyocytes and cardiac fibroblasts of neonatal rats...
November 22, 2017: International Heart Journal
https://www.readbyqxmd.com/read/29161764/mechanism-of-doxorubicin-cardiotoxicity-evaluated-by-integrating-multiple-molecular-effects-into-a-biophysical-model
#2
M Fernandez-Chas, M J Curtis, S A Niederer
BACKGROUND AND PURPOSE: Doxorubicin (DOX) is an effective cancer therapeutic agent but causes therapy-limiting cardiotoxicity. The effects of DOX and its metabolite doxorubicinol (DOXL) on individual channels have been well characterised in isolation. However, it is unknown how the action and interaction of affected channels combine to generate the phenotypic cardiotoxic outcome. We sought to develop an in silico model that links drug effects on channels to action potential duration (APD) and intracellular Ca(2+) concentration in order to address this gap in knowledge...
November 21, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29157865/peptide-yy-3-36-modulates-intracellular-calcium-through-activation-of-the-phosphatidylinositol-pathway-in-hippocampal-neurons
#3
Michelle Flores Domingues, Dênis Reis de Assis, Angela Regina Piovesan, Cháriston André Dal Belo, Jaderson Costa da Costa
Peptide YY (PYY) belongs to the neuropeptide Y (NPY) family, which also includes the pancreatic polypeptide (PP) and NPY. PYY is secreted by the intestinal L cells, being present in the blood stream in two active forms capable of crossing the blood brain barrier, PYY (1-36) and its cleavage product, PYY (3-36). PYY is a selective agonist for the Y2 receptor (Y2R) and these receptors are abundant in the hippocampus. Here we investigated the mechanisms by which PYY (3-36) regulates intracellular Ca(2+) concentrations ([Ca(2+)]i) in hippocampal neurons by employing a calcium imaging technique in hippocampal cultures...
November 7, 2017: Neuropeptides
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
#4
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
#5
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/29146527/osthole-attenuates-right-ventricular-remodeling-via-decreased-myocardial-apoptosis-and-inflammation-in-monocrotaline-induced-rats
#6
Yeli Li, Yiqi Li, Fuguo Shi, Lina Wang, Lisheng Li, Danli Yang
Osthole (Ost) is a coumarin that exhibits wide pharmacological effects in the cardiovascular system. However, whether Ost can inhibit apoptosis and inflammation in right ventricle (RV) cardiomyocytes and prevent RV remodeling is not clear. This study was designed to investigate the effect of Ost on RV remodeling and the underlying mechanism. By applying a monocrotaline (MCT)-induced rat model, the effect of Ost on RV remodeling was investigated. Rats were given a single dose of MCT (50mg⁄kg) subcutaneously (s...
November 13, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29145451/stromal-interaction-molecule-1-haploinsufficiency-causes-maladaptive-response-to-pressure-overload
#7
Takayoshi Ohba, Hiroyuki Watanabe, Manabu Murakami, Kenji Iino, Takeshi Adachi, Yoshihiro Baba, Tomohiro Kurosaki, Kyoichi Ono, Hiroshi Ito
Stromal interaction molecule 1 (STIM1), an endo/sarcoplasmic reticulum Ca2+ sensor, has been shown to control a Ca2+-dependent signal that promotes cardiac hypertrophy. However, whether STIM1 has adaptive role that helps to protect against cardiac overload stress remains unknown. We hypothesized that STIM1 deficiency causes a maladaptive response to pressure overload stress. We investigated STIM1 heterozygous KO (STIM1+/-) mice hearts, in which STIM1 protein levels decreased to 27% of wild-type (WT) with no compensatory increase in STIM2...
2017: PloS One
https://www.readbyqxmd.com/read/29145393/estimating-the-probabilities-of-rare-arrhythmic-events-in-multiscale-computational-models-of-cardiac-cells-and-tissue
#8
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/29141547/cardioprotective-effects-of-serca2a-overexpression-against-ischemia-reperfusion-induced-injuries-in-rats
#9
Yan Jian, Li-Li Tian, Lin-Hui Wang, Xiao-Dong Zhao, Jing-Wei Chen, Koji Murao, Wei Zhu, Liang Dong, Guo-Qing Wang, Wan-Ping Sun, Guo-Xing Zhang
AIMS: The aim of the present study is to assess how genetically increased Sarcoplasmic reticulum Ca2+-ATPase (Serca2a) expression affects cardiac injury after ischemia/reperfusion (I/R) exposure and the related mechanisms involved. METHODS AND RESULTS: Rats were subjected to left anterior descending coronary artery (LAD) occlusion for 30 min followed by a 24-hour reperfusion. Cardiac function analysis revealed that cardiac function dramatically improved in Serca2a transgenic rats (Serca2aTG) rats compared to wild type (WT) rats...
November 10, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/29137481/effects-of-pioglitazone-on-ventricular-myocyte-shortening-and-ca-2-transport-in-the-goto-kakizaki-type-2-diabetic-rat
#10
K A Salem, V Sydorenko, M Qureshi, M Oz, F C Howarth
Pioglitazone (PIO) is a thiazolidindione antidiabetic agent which improves insulin sensitivity and reduces blood glucose in experimental animals and treated patients. At the cellular level the actions of PIO in diabetic heart are poorly understood. A previous study has demonstrated shortened action potential duration and inhibition of a variety of transmembrane currents including L-type Ca(2+) current in normal canine ventricular myocytes. The effects of PIO on shortening and calcium transport in ventricular myocytes from the Goto-Kakizaki (GK) type 2 diabetic rat have been investigated...
November 10, 2017: Physiological Research
https://www.readbyqxmd.com/read/29136777/anti-hypertensive-and-vasodilatory-effects-of-amended-banxia-baizhu-tianma-tang
#11
Chu Shan Tan, Yean Chun Loh, Chiew Hoong Ng, Yung Sing Ch'ng, Mohd Zaini Asmawi, Mariam Ahmad, Mun Fei Yam
Although Banxia Baizhu Tianma Tang (BBT) has been long administered for hypertensive treatment in Traditional Chinese Medicine (TCM), the ratio of the herbal components that makes up the formulation has not been optimized with respect to the anti-hypertensive effect that it inherently possesses. A newly amended BBT (ABBT) formulation was developed using the evidence-based approach of orthogonal stimulus-response compatibility model. The ABBT showed enhanced therapeutic effect while maintaining its traditional theoretical approach rooted in TCM...
November 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29135437/an-adaptation-of-astronomical-image-processing-enables-characterization-and-functional-3d-mapping-of-individual-sites-of-excitation-contraction-coupling-in-rat-cardiac-muscle
#12
Qinghai Tian, Lars Kaestner, Laura Schröder, Jia Guo, Peter Lipp
In beating cardiomyocytes, synchronized localized Ca(2+) transients from thousands of active excitation-contraction coupling sites (ECC couplons) comprising plasma and sarcoplasmic reticulum membrane calcium channels are important determinants of the heart's performance. Nevertheless, our knowledge about their properties is limited by the lack of appropriate experimental and analysis strategies. We designed CaCLEAN to untangle fundamental characteristics of ECC couplons by combining the astronomer's CLEAN algorithm with known properties of calcium diffusion...
November 14, 2017: ELife
https://www.readbyqxmd.com/read/29130489/angiotensin-1-7-modulates-electrophysiological-characteristics-and-calcium-homeostasis-in-pulmonary-veins-cardiomyocytes-via-mas-pi3k-enos-signaling-pathway
#13
Yen-Yu Lu, Wen-Shiann Wu, Yung-Kuo Lin, Chen-Chuan Cheng, Yao-Chang Chen, Shih-Ann Chen, Yi-Jen Chen
BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia, and pulmonary veins (PVs) play a critical role in triggering AF. Angiotensin (Ang)-(1-7) regulates calcium (Ca(2+) ) homeostasis and also plays a critical role in cardiovascular pathophysiology. However, the role of Ang-(1-7) in PV arrhythmogenesis remains unclear. MATERIALS AND METHODS: Conventional microelectrodes, whole-cell patch-clamp, and the Fluo-3 fluorimetric ratio technique were used to record ionic currents and intracellular Ca(2+) in isolated rabbit PV preparations, and in single isolated PV cardiomyocytes, before and after administration of Ang-(1-7)...
November 12, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29123976/advanced-glycation-end-products-reduce-the-calcium-transient-in-cardiomyocytes-by-increasing-production-of-reactive-oxygen-species-and-nitric-oxide
#14
Zeinab Hegab, Tamer M A Mohamed, Nicholas Stafford, Mamas Mamas, Elizabeth J Cartwright, Delvac Oceandy
Advanced glycation end products (AGE) are central to the development of cardiovascular complications associated with diabetes mellitus. AGE may alter cellular function through cross-linking of cellular proteins or by activating the AGE receptor (RAGE). However, the signalling molecules involved during AGE stimulation in cardiomyocytes remain unclear. Here, we investigated the effects of AGE treatment on intracellular calcium homeostasis of isolated cardiomyocytes and studied the activation of signalling molecules involved in this process...
November 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/29122978/the-structural-basis-of-ryanodine-receptor-ion-channel-function
#15
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/29119399/green-tea-extract-increases-the-expression-of-genes-responsible-for-regulation-of-calcium-balance-in-rat-slow-twitch-muscles-under-conditions-of-exhausting-exercise
#16
E A Korf, I V Kubasov, M S Vonsky, A V Novozhilov, A L Runov, E V Kurchakova, E V Matrosova, T V Tavrovskaya, N V Goncharov
We studied the role of calcium-regulating structures of slow- (m. soleus, SOL) and fast-twitch (m. extensor digitorum longus, EDL) skeletal muscles of rats during adaptation to exhausting physical activity and the possibility of modulating this adaptation with decaffeinated green tea extract. It was established that EDL adaptation is mainly aimed at Са(2+) elimination from the sarcoplasm by Са-ATPase and its retention in the reticulum by calsequestrin. Administration of green tea extract increased endurance due to involvement of slow-twitch muscles whose adaptation is associated with enhanced expression of all the studied genes responsible for the regulation of Ca(2+) balance...
November 9, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29117223/sensitivity-analysis-revealing-the-effect-of-modulating-ionic-mechanisms-on-calcium-dynamics-in-simulated-human-heart-failure
#17
Maria T Mora, Jose M Ferrero, Lucia Romero, Beatriz Trenor
Abnormal intracellular Ca2+ handling is the major contributor to the depressed cardiac contractility observed in heart failure. The electrophysiological remodeling associated with this pathology alters both the action potential and the Ca2+ dynamics, leading to a defective excitation-contraction coupling that ends in mechanical dysfunction. The importance of maintaining a correct intracellular Ca2+ concentration requires a better understanding of its regulation by ionic mechanisms. To study the electrical activity and ionic homeostasis of failing myocytes, a modified version of the O'Hara et al...
2017: PloS One
https://www.readbyqxmd.com/read/29104955/crosstalk-between-mlo-y4-osteocytes-and-c2c12-muscle-cells-is-mediated-by-the-wnt-%C3%AE-catenin-pathway
#18
Jian Huang, Sandra Romero-Suarez, Nuria Lara, Chenglin Mo, Simon Kaja, Leticia Brotto, Sarah L Dallas, Mark L Johnson, Katharina Jähn, Lynda F Bonewald, Marco Brotto
We examined the effects of osteocyte secreted factors on myogenesis and muscle function. MLO-Y4 osteocyte-like cell conditioned media (CM) (10%) increased ex vivo soleus muscle contractile force by ~25%. MLO-Y4 and primary osteocyte CM (1-10%) stimulated myogenic differentiation of C2C12 myoblasts, but 10% osteoblast CMs did not enhance C2C12 cell differentiation. Since WNT3a and WNT1 are secreted by osteocytes, and the expression level of Wnt3a is increased in MLO-Y4 cells by fluid flow shear stress, both were compared, showing WNT3a more potent than WNT1 in inducing myogenesis...
October 2017: JBMR Plus
https://www.readbyqxmd.com/read/29081402/conformational-memory-in-the-association-of-the-transmembrane-protein-phospholamban-with-the-sarcoplasmic-reticulum-calcium-pump-serca
#19
Serena Smeazzetto, Gareth P Armanious, Marai Rosa Moncelli, Jessi J Bak, M Joanne Lemieux, Howard S Young, Francesco Tadini-Buoninsegni
The sarcoplasmic reticulum Ca2+-ATPase SERCA promotes muscle relaxation by pumping calcium ions from the cytoplasm into the sarcoplasmic reticulum. SERCA activity is regulated by a variety of small transmembrane peptides, most notably by phospholamban in cardiac muscle and sarcolipin in skeletal muscle. However, how phospholamban and sarcolipin regulate SERCA is not fully understood. In the present study, we evaluated the effects of phospholamban and sarcolipin on calcium translocation and ATP hydrolysis by SERCA under conditions that mimic environments in sarcoplasmic reticulum membranes...
October 29, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29079778/exercise-dependent-formation-of-new-junctions-that-promote-stim1-orai1-assembly-in-skeletal-muscle
#20
Simona Boncompagni, Antonio Michelucci, Laura Pietrangelo, Robert T Dirksen, Feliciano Protasi
Store-operated Ca(2+) entry (SOCE), a ubiquitous mechanism that allows recovery of Ca(2+) ions from the extracellular space, has been proposed to limit fatigue during repetitive skeletal muscle activity. However, the subcellular location for SOCE in muscle fibers has not been unequivocally identified. Here we show that exercise drives a significant remodeling of the sarcotubular system to form previously unidentified junctions between the sarcoplasmic reticulum (SR) and transverse-tubules (TTs). We also demonstrate that these new SR-TT junctions contain the molecular machinery that mediate SOCE: stromal interaction molecule-1 (STIM1), which functions as the SR Ca(2+) sensor, and Orai1, the Ca(2+)-permeable channel in the TT...
October 27, 2017: Scientific Reports
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