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phospholamban

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https://www.readbyqxmd.com/read/28734932/a-pyridone-derivative-activates-serca2a-by-attenuating-the-inhibitory-effect-of-phospholamban
#1
Manami Kaneko, Hisato Yamamoto, Hiroki Sakai, Yusuke Kamada, Toshiki Tanaka, Shuji Fujiwara, Synsuke Yamamoto, Hiroki Takahagi, Hideyuki Igawa, Shizuo Kasai, Masakuni Noda, Makoto Inui, Tomoyuki Nishimoto
The cardiac sarco/endoplasmic reticulum Ca(2+)-dependent ATPase 2a (SERCA2a) plays a central role in Ca(2+) handling within cardiomyocytes and is negatively regulated by phospholamban (PLN), a sarcoplasmic reticulum (SR) membrane protein. The activation of SERCA2a, which has been reported to improve cardiac dysfunction in heart failure, is a potential therapeutic approach for heart failure. Therefore, we developed a novel small molecule, compound A and characterized it both in vitro and in vivo. Compound A activated the Ca(2+)-dependent ATPase activity of cardiac SR vesicles but not that of skeletal muscle SR vesicles that lack PLN...
July 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28698769/high-intensity-exercise-reduces-cardiac-fibrosis-and-hypertrophy-but-does-not-restore-the-nitroso-redox-imbalance-in-diabetic-cardiomyopathy
#2
Ulises Novoa, Diego Arauna, Marisol Moran, Madelaine Nuñez, Sebastián Zagmutt, Sergio Saldivia, Cristian Valdes, Jorge Villaseñor, Carmen Gloria Zambrano, Daniel R Gonzalez
Diabetic cardiomyopathy refers to the manifestations in the heart as a result of altered glucose homeostasis, reflected as fibrosis, cellular hypertrophy, increased oxidative stress, and apoptosis, leading to ventricular dysfunction. Since physical exercise has been indicated as cardioprotective, we tested the hypothesis that high-intensity exercise training could reverse the cardiac maladaptations produced by diabetes. For this, diabetes was induced in rats by a single dose of alloxan. Diabetic rats were randomly assigned to a sedentary group or submitted to a program of exercise on a treadmill for 4 weeks at 80% of maximal performance...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28698617/loss-of-md1-exacerbates-pressure-overload-induced-left-ventricular-structural-and-electrical-remodelling
#3
Jianye Peng, Yu Liu, Xiaoju Xiong, Congxin Huang, Yang Mei, Zhiqiang Wang, Yanhong Tang, Jing Ye, Bin Kong, Wanli Liu, Teng Wang, He Huang
Myeloid differentiation protein 1 (MD1) has been implicated in numerous pathophysiological processes, including immune regulation, obesity, insulin resistance, and inflammation. However, the role of MD1 in cardiac remodelling remains incompletely understood. We used MD1-knockout (KO) mice and their wild-type littermates to determine the functional significance of MD1 in the regulation of aortic banding (AB)-induced left ventricular (LV) structural and electrical remodelling and its underlying mechanisms. After 4 weeks of AB, MD1-KO hearts showed substantial aggravation of LV hypertrophy, fibrosis, LV dilation and dysfunction, and electrical remodelling, which resulted in overt heart failure and increased electrophysiological instability...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28683791/in-vivo-administration-of-urolithin-a-and-b-prevents-the-occurrence-of-cardiac-dysfunction-in-streptozotocin-induced-diabetic-rats
#4
Monia Savi, Leonardo Bocchi, Pedro Mena, Margherita Dall'Asta, Alan Crozier, Furio Brighenti, Donatella Stilli, Daniele Del Rio
BACKGROUND: Emerging evidence suggests that specific (poly)phenols may constitute new preventative strategies to counteract cell oxidative stress and myocardial tissue inflammation, which have a key role in the patho-physiology of diabetic cardiomyopathy. In a rat model of early diabetes, we evaluated whether in vivo administration of urolithin A (UA) or urolithin B (UB), the main gut microbiota phenolic metabolites of ellagitannin-rich foods, can reduce diabetes-induced microenvironmental changes in myocardial tissue, preventing cardiac functional impairment...
July 6, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28665545/inhibition-of-mevalonate-pathway-prevents-ischemia-induced-cardiac-dysfunction-in-rats-via-rhoa-independent-signaling-pathway
#5
Ying Yang, Xiqing Rong, Xue Lv, Wenbing Jiang, Yuan Yang, Dongwu Lai, Shiming Xu, Guosheng Fu
AIM: We previously demonstrated that anoxia-mediated Ca(2+) handling dysfunction could be ameliorated through inhibition of mevalonate pathway via RhoA- and Ras-related mechanisms in H9c2 cells. In this study, we further explored whether inhibition of mevalonate pathway is associated with cardiac remodeling and dysfunction in ischemic cardiomyopathy, and discuss the possible role of Ras, Rac and RhoA in cardiac dysfunction. METHODS: We investigated the role of mevalonate pathway in cardiac remodeling and cardiomyocyte Ca(2+) handling proteins expression in a rat model of cardiac dysfunction due to myocardial infarction (MI)...
June 30, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28656205/role-of-pka-in-the-process-of-neonatal-cardiomyocyte-hypertrophy-induced-by-urotensin%C3%A2-ii
#6
Jianrong Xu, Qinghua Han, Hongtao Shi, Wenyuan Liu, Tingting Chu, Hao Li
The model of urotensin II (UII)-induced cardiomyocyte hypertrophy has been widely used in studies on hypertrophy. However, the molecular mechanisms responsible for UII-induced cardiomyocyte hypertrophy have not yet been fully elucidated. It has been demonstrated that cardiomyocyte hypertrophy induced by UII is associated with changes in the intracellular Ca2+ concentration. In the present study, we investigated whether the cAMP-dependent protein kinase A (PKA)‑mediated upregulation of the phosphorylation levels of phospholamban (PLN) at Ser16 contributes to UII-induced cardiomyocyte hypertrophy...
June 22, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28655649/interregional-electro-mechanical-heterogeneity-in-the-rabbit-myocardium
#7
REVIEW
Franz F Dressler, Ilona Bodi, Marius Menza, Robin Moss, Heiko Bugger, Christoph Bode, Jan C Behrends, Gunnar Seemann, Katja E Odening
BACKGROUND: Increased electrical heterogeneity has been causatively linked to arrhythmic disorders, yet the knowledge about physiological heterogeneity remains incomplete. This study investigates regional electro-mechanical heterogeneities in rabbits, one of the key animal models for arrhythmic disorders. METHODS AND FINDINGS: 7 wild-type rabbits were examined by phase-contrast magnetic resonance imaging in vivo to assess cardiac wall movement velocities. Using a novel data-processing algorithm regional contraction-like profiles were calculated...
June 24, 2017: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/28649129/c33-s-a-novel-pde9a-inhibitor-protects-against-rat-cardiac-hypertrophy-through-upregulating-cgmp-signaling
#8
Pan-Xia Wang, Zhuo-Ming Li, Si-Dong Cai, Jing-Yan Li, Ping He, Yi Huang, Guo-Shuai Feng, Hai-Bin Luo, Shao-Rui Chen, Pei-Qing Liu
Phosphodiesterase-9A (PDE9A) expression is upregulated during cardiac hypertrophy and heart failure. Accumulating evidence suggests that PDE9A might be a promising therapeutic target for heart diseases. The present study sought to investigate the effects and underlying mechanisms of C33(S), a novel selective PDE9A inhibitor, on cardiac hypertrophy in vitro and in vivo. Treatment of neonatal rat cardiomyocytes (NRCMs) with PE (100 μmol/L) or ISO (1 μmol/L) induced cardiac hypertrophy characterized by significantly increased cell surface areas and increased expression of fetal genes (ANF and BNP)...
June 26, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28643218/empagliflozin-improves-left-ventricular-diastolic-dysfunction-in-a-genetic-model-of-type-2-diabetes
#9
Nadjib Hammoudi, Dongtak Jeong, Rajvir Singh, Ahmed Farhat, Michel Komajda, Eric Mayoux, Roger Hajjar, Djamel Lebeche
PURPOSE: Cardiovascular (CV) diseases in type 2 diabetes (T2DM) represent an enormous burden with high mortality and morbidity. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently emerged as a new antidiabetic class that improves glucose control, as well as body weight and blood pressure with no increased risk of hypoglycemia. The first CV outcome study terminated with empagliflozin, a specific SGLT2 inhibitor, has shown a reduction in CV mortality and in heart failure hospitalization, suggesting a beneficial impact on cardiac function which remains to be demonstrated...
June 22, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28640447/role-of-serca-pump-in-muscle-thermogenesis-and-metabolism
#10
Muthu Periasamy, Santosh Kumar Maurya, Sanjaya Kumar Sahoo, Sushant Singh, Sanjaya Kumar Sahoo, Felipe C G Reis, Naresh Chandra Bal
In muscle cells, the sarcoplasmic reticulum (SR) not only acts as a Ca2+ store, but also regulates the contractile characteristics of the muscle. Ca2+ release from the SR is the primary mechanism for activating muscle contraction and reuptake of Ca2+ by the sarcoplasmic reticulum Ca2+ ATPase (SERCA) pump causes muscle relaxation. The SERCA pump isoforms are encoded by three genes, SERCA 1, 2, and 3, which are differentially expressed in muscle and determine SR Ca2+ dynamics by affecting the rate and amount of Ca2+ uptake, thereby affecting SR store and release of Ca2+ in muscle...
June 18, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28630914/deregulated-ca-2-cycling-underlies-the-development-of-arrhythmia-and-heart-disease-due-to-mutant-obscurin
#11
Li-Yen R Hu, Maegen A Ackermann, Peter A Hecker, Benjamin L Prosser, Brendan King, Kelly A O'Connell, Alyssa Grogan, Logan C Meyer, Christopher E Berndsen, Nathan T Wright, W Jonathan Lederer, Aikaterini Kontrogianni-Konstantopoulos
Obscurins are cytoskeletal proteins with structural and regulatory roles encoded by OBSCN. Mutations in OBSCN are associated with the development of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Specifically, the R4344Q mutation present in immunoglobulin domain 58 (Ig58) was the first to be linked with the development of HCM. To assess the effects of R4344Q in vivo, we generated the respective knock-in mouse model. Mutant obscurins are expressed and incorporated normally into sarcomeres...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28619984/mitochondrial-integrity-and-function-in-the-progression-of-early-pressure-overload-induced-left-ventricular-remodeling
#12
Antoine H Chaanine, K Sreekumaran Nair, Robert H Bergen, Katherine Klaus, Adam J Guenzel, Roger J Hajjar, Margaret M Redfield
BACKGROUND: Following pressure overload, compensatory concentric left ventricular remodeling (CR) variably transitions to eccentric remodeling (ER) and systolic dysfunction. Mechanisms responsible for this transition are incompletely understood. Here we leverage phenotypic variability in pressure overload-induced cardiac remodeling to test the hypothesis that altered mitochondrial homeostasis and calcium handling occur early in the transition from CR to ER, before overt systolic dysfunction...
June 15, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28573136/effects-of-wenxin-keli-on-cardiac-hypertrophy-and-arrhythmia-via-regulation-of-the-calcium-calmodulin-dependent-kinase-ii-signaling-pathway
#13
Xinyu Yang, Yu Chen, Yanda Li, Xiaomeng Ren, Yanwei Xing, Hongcai Shang
We investigated the effects of Wenxin Keli (WXKL) on the Calcium/Calmodulin dependent kinase II (CaMK II) signal transduction pathway with transverse aortic constriction (TAC) rats. Echocardiographic measurements were obtained 3 and 9 weeks after the surgery. Meanwhile, the action potentials (APDs) were recorded using the whole-cell patch clamp technique, and western blotting was used to assess components of the CaMK II signal transduction pathway. At both 3 and 9 weeks after treatment, the fractional shortening (FS%) increased in the WXKL group compared with the TAC group...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28572573/protein-tyrosine-phosphatase-1b-is-a-mediator-of-cyclic-adp-ribose-induced-ca-2-signaling-in-ventricular-myocytes
#14
Seon-Ah Park, Bing-Zhe Hong, Ki-Chan Ha, Uh-Hyun Kim, Myung-Kwan Han, Yong-Geun Kwak
Cyclic ADP-ribose (cADPR) releases Ca(2+) from ryanodine receptor (RyR)-sensitive calcium pools in various cell types. In cardiac myocytes, the physiological levels of cADPR transiently increase the amplitude and frequency of Ca(2+) (that is, a rapid increase and decrease of calcium within one second) during the cardiac action potential. In this study, we demonstrated that cADPR levels higher than physiological levels induce a slow and gradual increase in the resting intracellular Ca(2+) ([Ca(2+)]i) level over 10 min by inhibiting the sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA)...
June 2, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28533073/the-impact-of-sevoflurane-on-coupling-of-the-left-ventricular-to-systemic-vasculature-in-rats-with-chronic-pulmonary-hypertension
#15
Lu Wang, Hui Luo, Gang Qin, Yanan Cao, Xiaowei Gao, Zhong Zhang, Zhi Ye, Junjie Zhang, Qulian Guo, E Wang
OBJECTIVES: The relationship between left ventricular function and afterload has not been investigated as much as the right ventricular function under chronic pulmonary hypertension (PH) during anesthesia. This study was designed to investigate effects of sevoflurane on the intrinsic coupling relationship between the left ventricle and systemic vasculature in the presence of PH. DESIGN: A randomized, controlled study. SETTING: University hospital...
February 13, 2017: Journal of Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/28526544/interleukin-18-gene-deletion-protects-against-sepsis-induced-cardiac-dysfunction-by-inhibiting-pp2a-activity
#16
Yoshitaka Okuhara, Shunichi Yokoe, Toshihiro Iwasaku, Akiyo Eguchi, Koichi Nishimura, Wen Li, Makiko Oboshi, Yoshiro Naito, Toshiaki Mano, Michio Asahi, Haruki Okamura, Tohru Masuyama, Shinichi Hirotani
BACKGROUND: Interleukin-18 (IL-18) neutralization protects against lipopolysaccharide (LPS)-induced injuries, including myocardial dysfunction. However, the mechanism is yet to be fully elucidated. The aim of the present study was to determine whether IL-18 gene deletion prevents sepsis-induced cardiac dysfunction and to elucidate the potential mechanisms underlying IL-18-mediated cardiotoxicity by LPS. METHODS AND RESULTS: Ten-week-old male wild-type (WT) and IL-18 knockout (IL-18 KO) mice were intraperitoneally administered LPS...
May 4, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28500853/protective-effects-of-circulating-microvesicles-derived-from-myocardial-ischemic-rats-on-apoptosis-of-cardiomyocytes-in-myocardial-ischemia-reperfusion-injury
#17
Yao Wang, Su Wei, Yi-Lu Wang, Miao Liu, Man Shang, Qi Zhang, Yan-Na Wu, Ming-Lin Liu, Jun-Qiu Song, Yan-Xia Liu
OBJECTIVE: To investigate the effects of circulating microvesicles derived from myocardial ischemia (I-MVs) on apoptosis in myocardial ischemia/reperfusion (I/R) injury in rats. METHODS: I-MVs from rats undergoing myocardial left anterior descending (LAD) coronary artery ligation were isolated by ultracentrifugation from circulating blood and characterized by flow cytometry. I-MVs were administered intravenously (4.8 mg/kg) at 5 min before reperfusion procedure in I/R injury model which was induced by 30-min of ischemia and 120-min of reperfusion of LAD in rats...
April 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28497395/cardio-protective-effects-of-qishen-granule-on-sarcoplasmic-reticulum-ca-2-handling-in-heart-failure-rats
#18
Ling-Hui Lu, Chun Li, Qi-Yan Wang, Qian Zhang, Yi Zhang, Hui Meng, Yong Wang, Wei Wang
OBJECTIVES: To assess the effects of Qishen Granule (, QSG) on sarcoplasmic reticulum (SR) Ca(2+) handling in heart failure (HF) model of rats and to explore the underlying molecular mechanisms. METHODS: HF rat models were induced by left anterior descending coronary artery ligation surgery and high-fat diet feeding. Rats were randomly divided into sham (n=10), model (n=10), QSG (n=12, 2.2 g/kg daily) and metoprolol groups (n=12, 10.5 mg/kg daily). The therapeutic effects of QSG were evaluated by echocardiography and blood lipid testing...
May 11, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28487373/interactions-between-small-ankyrin-1-and-sarcolipin-coordinately-regulate-activity-of-the-sarco-endo-plasmic-reticulum-ca-2-atpase-serca1
#19
Patrick F Desmond, Amanda Labuza, Joaquin Muriel, Michele L Markwardt, Allison E Mancini, Mark A Rizzo, Robert J Bloch
SERCA1, the sarco(endo)plasmic reticulum Ca(2+)-ATPase of skeletal muscle, is essential for muscle relaxation and maintenance of low resting Ca(2+) levels in the myoplasm. We recently reported that small ankyrin 1 (sAnk1) interacts with the sarco(endo)plasmic reticulum Ca(2+)-ATPase in skeletal muscle (SERCA1) to inhibit its activity. We also showed that this interaction is mediated at least in part through sAnk1's transmembrane domain in a manner similar to that of sarcolipin (SLN). Earlier studies have shown that SLN and phospholamban, the other well studied small SERCA-regulatory proteins, oligomerize either alone or together...
June 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28487342/calcium-calmodulin-dependent-protein-kinase-ii-activity-persists-during-chronic-%C3%AE-adrenoceptor-blockade-in-experimental-and-human-heart-failure
#20
Matthias Dewenter, Stefan Neef, Christiane Vettel, Simon Lämmle, Christina Beushausen, Laura C Zelarayan, Sylvia Katz, Albert von der Lieth, Stefanie Meyer-Roxlau, Silvio Weber, Thomas Wieland, Samuel Sossalla, Johannes Backs, Joan H Brown, Lars S Maier, Ali El-Armouche
BACKGROUND: Considerable evidence suggests that calcium/calmodulin-dependent protein kinase II (CaMKII) overactivity plays a crucial role in the pathophysiology of heart failure (HF), a condition characterized by excessive β-adrenoceptor (β-AR) stimulation. Recent studies indicate a significant cross talk between β-AR signaling and CaMKII activation presenting CaMKII as a possible downstream mediator of detrimental β-AR signaling in HF. In this study, we investigated the effect of chronic β-AR blocker treatment on CaMKII activity in human and experimental HF...
May 2017: Circulation. Heart Failure
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