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https://www.readbyqxmd.com/read/28735292/pathogenesis-of-hypertrophic-cardiomyopathy-is-mutation-rather-than-disease-specific-a-comparison-of-the-cardiac-troponin-t-e163r-and-r92q-mouse-models
#1
Cecilia Ferrantini, Raffaele Coppini, Josè Manuel Pioner, Francesca Gentile, Benedetta Tosi, Luca Mazzoni, Beatrice Scellini, Nicoletta Piroddi, Annunziatina Laurino, Lorenzo Santini, Valentina Spinelli, Leonardo Sacconi, Pieter De Tombe, Rachel Moore, Jil Tardiff, Alessandro Mugelli, Iacopo Olivotto, Elisabetta Cerbai, Chiara Tesi, Corrado Poggesi
BACKGROUND: In cardiomyocytes from patients with hypertrophic cardiomyopathy, mechanical dysfunction and arrhythmogenicity are caused by mutation-driven changes in myofilament function combined with excitation-contraction (E-C) coupling abnormalities related to adverse remodeling. Whether myofilament or E-C coupling alterations are more relevant in disease development is unknown. Here, we aim to investigate whether the relative roles of myofilament dysfunction and E-C coupling remodeling in determining the hypertrophic cardiomyopathy phenotype are mutation specific...
July 22, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28734932/a-pyridone-derivative-activates-serca2a-by-attenuating-the-inhibitory-effect-of-phospholamban
#2
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/28728119/nf-%C3%AE%C2%BAb-mediated-inflammation-correlates-with-calcium-overload-under-arsenic-trioxide-induced-myocardial-damage-in-gallus-gallus
#3
Siwen Li, Yu Wang, Hongjing Zhao, Ying He, Jinglun Li, Guangshun Jiang, Mingwei Xing
Arsenic is a known environmental pollutant and highly hazardous toxin to human health. Due to the biological accumulation, arsenic produces a variety of cardiovascular diseases. However, the exact mechanism is still unclear. Here, our objective was to evaluate myocardial damage and determine the potential mechanism under arsenic exposure in chickens. Arsenic trioxide (As2O3) (1.25 mg/kg BW, corresponding 15 mg/kg feed) was administered as basal diet to male Hy-line chickens (one-day-old) for 4, 8 and 12 weeks...
July 14, 2017: Chemosphere
https://www.readbyqxmd.com/read/28727756/dysregulation-of-micrornas-and-renin-angiotensin-system-in-high-salt-diet-induced-cardiac-dysfunction-in-uninephrectomized-rats
#4
Venkateswara Rao Amara, Sunil Kumar Surapaneni, Kulbhushan Tikoo
Uninephrectomy is not associated with major adverse events in cardiovascular and renal functions of live kidney donors. The effect of high salt diet on the quality of life of live kidney donors is largely unknown. Hence in this study, we aimed to determine the effect of high salt diet on the alterations of renin-angiotensin system and microRNAs leading to CV and renal dysfunction in uninephrectomized rats. In order to mimic clinical scenario, uninephrectomized male Sprague Dawley rats were fed initially with normal pellet diet for 12 weeks and then for 20 weeks with high salt (10% w/w NaCl) diet...
2017: PloS One
https://www.readbyqxmd.com/read/28717166/targeting-cellular-calcium-homeostasis-to-prevent-cytokine-mediated-beta-cell-death
#5
Amy L Clark, Kohsuke Kanekura, Zeno Lavagnino, Larry D Spears, Damien Abreu, Jana Mahadevan, Takuya Yagi, Clay F Semenkovich, David W Piston, Fumihiko Urano
Pro-inflammatory cytokines are important mediators of islet inflammation, leading to beta cell death in type 1 diabetes. Although alterations in both endoplasmic reticulum (ER) and cytosolic free calcium levels are known to play a role in cytokine-mediated beta cell death, there are currently no treatments targeting cellular calcium homeostasis to combat type 1 diabetes. Here we show that modulation of cellular calcium homeostasis can mitigate cytokine- and ER stress-mediated beta cell death. The calcium modulating compounds, dantrolene and sitagliptin, both prevent cytokine and ER stress-induced activation of the pro-apoptotic calcium-dependent enzyme, calpain, and partly suppress beta cell death in INS1E cells and human primary islets...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28713824/effects-of-hyperglycemia-on-vascular-smooth-muscle-ca-2-signaling
#6
Nahed El-Najjar, Rashmi P Kulkarni, Nancy Nader, Rawad Hodeify, Khaled Machaca
Diabetes is a complex disease that is characterized with hyperglycemia, dyslipidemia, and insulin resistance. These pathologies are associated with significant cardiovascular implications that affect both the macro- and microvasculature. It is therefore important to understand the effects of various pathologies associated with diabetes on the vasculature. Here we directly test the effects of hyperglycemia on vascular smooth muscle (VSM) Ca(2+) signaling in an isolated in vitro system using the A7r5 rat aortic cell line as a model...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28713161/functional-expression-of-the-ca-2-signaling-machinery-in-human-embryonic-stem-cells
#7
Ji-Jun Huang, Yi-Jie Wang, Min Zhang, Peng Zhang, He Liang, Hua-Jun Bai, Xiu-Jian Yu, Huang-Tian Yang
Emerging evidence suggests that Ca(2+) signals are important for the self-renewal and differentiation of human embryonic stem cells (hESCs). However, little is known about the physiological and pharmacological properties of the Ca(2+)-handling machinery in hESCs. In this study we used RT-PCR and Western blotting to analyze the expression profiles of genes encoding Ca(2+)-handling proteins; we also used confocal Ca(2+) imaging and pharmacological approaches to determine the contribution of the Ca(2+)-handling machinery to the regulation of Ca(2+) signaling in hESCs...
July 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28695302/argatroban-attenuates-diabetic-cardiomyopathy-in-rats-by-reducing-fibrosis-inflammation-apoptosis-and-protease-activated-receptor-expression
#8
Yogesh Bulani, Shyam Sunder Sharma
PURPOSE: Chronic diabetes is associated with cardiovascular dysfunctions. Diabetic cardiomyopathy (DCM) is one of the serious cardiovascular complications associated with diabetes. Despite significant efforts in understanding the pathophysiology of DCM, management of DCM is not adequate due to its complex pathophysiology. Recently, involvement of protease-activated receptors (PARs) has been postulated in cardiovascular diseases. These receptors are activated by thrombin, trypsin, or other serine proteases...
July 10, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28670281/n-desmethyldauricine-induces-autophagic-cell-death-in-apoptosis-defective-cells-via-ca-2-mobilization
#9
Betty Y K Law, Simon W F Mok, Juan Chen, Francesco Michelangeli, Zhi-Hong Jiang, Yu Han, Yuan Q Qu, Alena C L Qiu, Su-Wei Xu, Wei-Wei Xue, Xiao-Jun Yao, Jia Y Gao, Masood-Ul-Hassan Javed, Paolo Coghi, Liang Liu, Vincent K W Wong
Resistance of cancer cells to chemotherapy remains a significant problem in oncology. Mechanisms regulating programmed cell death, including apoptosis, autophagy or necrosis, in the treatment of cancers have been extensively investigated over the last few decades. Autophagy is now emerging as an important pathway in regulating cell death or survival in cancer therapy. Recent studies demonstrated variety of natural small-molecules could induce autophagic cell death in apoptosis-resistant cancer cells, therefore, discovery of novel autophagic enhancers from natural products could be a promising strategy for treatment of chemotherapy-resistant cancer...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28665545/inhibition-of-mevalonate-pathway-prevents-ischemia-induced-cardiac-dysfunction-in-rats-via-rhoa-independent-signaling-pathway
#10
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
#11
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/28651627/induction-of-endoplasmic-reticulum-calcium-pump-expression-during-early-leukemic-b-cell-differentiation
#12
Lamia Aït Ghezali, Atousa Arbabian, Hervé Roudot, Jean-Philippe Brouland, Fanny Baran-Marszak, Evelyn Salvaris, Andrew Boyd, Hans G Drexler, Agnes Enyedi, Remi Letestu, Nadine Varin-Blank, Bela Papp
BACKGROUND: Endoplasmic reticulum (ER) calcium storage and release play important roles in B lymphocyte maturation, survival, antigen-dependent cell activation and immunoglobulin synthesis. Calcium is accumulated in the endoplasmic reticulum (ER) by Sarco/Endoplasmic Reticulum Calcium ATPases (SERCA enzymes). Because lymphocyte function is critically dependent on SERCA activity, it is important to understand qualitative and quantitative changes of SERCA protein expression that occur during B lymphoid differentiation and leukemogenesis...
June 26, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28649039/pm2-5-exposure-in-utero-contributes-to-neonatal-cardiac-dysfunction-in-mice
#13
Vineeta Tanwar, Jeremy M Adelstein, Jacob A Grimmer, Dane J Youtz, Benjamin P Sugar, Loren E Wold
OBJECTIVE: Exposure of fine particulate matter (PM2.5) to pregnant dams has been shown to be strongly associated with adverse cardiovascular outcomes in offspring at adulthood, however, effects evident during neonatal periods are unclear. We designed this study to examine cardiac function of neonatal mice (14 days old) exposed to in utero PM2.5. METHODS: Pregnant FVB female mice were exposed either to filtered air (FA) or PM2.5 at an average concentration of 91...
June 22, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28648117/alteration-of-sarcoplasmic-reticulum-ca-2-atpase-expression-in-lower-limb-ischemia-caused-by-atherosclerosis-obliterans
#14
J Fodor, A Gomba-Tóth, T Oláh, E Zádor, Zs Cs Tóth, I Ioannis, B Molnár, I Kovács, L Csernoch
Atherosclerosis is a disease caused by a build-up of fatty plaques and cholesterol in the arteries. The lumen of the vessels is obliterated resulting in restricted blood supply to tissues. In ischemic conditions, the cytosolic Ca(2+) level of skeletal muscle may increase, indicating the alteration of Ca(2+) removal mechanisms. Ca(2+) is transported from cytosol into the sarcoplasmic reticulum by Ca(2+) ATPase (SERCA), with its 1a isoform expressed in adult, while its 1b isoform in neonatal and regenerating fast-twitch skeletal muscle...
June 26, 2017: Physiology International
https://www.readbyqxmd.com/read/28642329/experimental-and-computational-insight-into-human-mesenchymal-stem-cell-paracrine-signaling-and-heterocellular-coupling-effects-on-cardiac-contractility-and-arrhythmogenicity
#15
Joshua Mayourian, Timothy J Cashman, Delaine K Ceholski, Bryce V Johnson, David Sachs, Deepak A Kaji, Susmita Sahoo, Joshua M Hare, Roger J Hajjar, Eric A Sobie, Kevin D Costa
Rationale: Myocardial delivery of human mesenchymal stem cells (hMSCs) is an emerging therapy for treating the failing heart. However, the relative effects of hMSC-mediated heterocellular coupling (HC) and paracrine signaling (PS) on human cardiac contractility and arrhythmogenicity remain unresolved. Objective: To better understand hMSC PS and HC effects on human cardiac contractility and arrhythmogenicity by integrating experimental and computational approaches. Methods and Results: : Extending our previous hMSC-cardiomyocyte HC computational model, we incorporated experimentally calibrated hMSC PS effects on cardiomyocyte L-type calcium channel/SERCA activity and cardiac tissue fibrosis...
June 22, 2017: Circulation Research
https://www.readbyqxmd.com/read/28640447/role-of-serca-pump-in-muscle-thermogenesis-and-metabolism
#16
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/28636017/effect-of-cisplatin-on-the-transport-activity-of-pii-type-atpases
#17
Francesco Tadini-Buoninsegni, Giacomo Sordi, Serena Smeazzetto, Giovanni Natile, Fabio Arnesano
Cisplatin (cis-diamminedichlorido-Pt(ii)) is extensively used as a chemotherapeutic agent against various types of tumors. However, cisplatin administration causes serious side effects, including nephrotoxicity, ototoxicity and neurotoxicity. It has been shown that cisplatin can interact with P-type ATPases, e.g., Cu(+)-ATPases (ATP7A and ATP7B) and Na(+),K(+)-ATPase. Cisplatin-induced inhibition of Na(+),K(+)-ATPase has been related to the nephrotoxic effect of the drug. To investigate the inhibitory effects of cisplatin on the pumping activity of PII-type ATPases, electrical measurements were performed on sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and Na(+),K(+)-ATPase embedded in vesicles/membrane fragments adsorbed on a solid-supported membrane...
July 19, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28617952/systolic-ca-2-i-regulates-diastolic-levels-in-rat-ventricular-myocytes
#18
Rajiv Sankaranarayanan, Kornél Kistamás, David J Greensmith, Luigi A Venetucci, David A Eisner
KEY POINTS: For the heart to function as a pump, intracellular calcium concentration ([Ca(2+) ]i ) must increase during systole to activate contraction and then fall, during diastole, to allow the myofilaments to relax and the heart to refill with blood. The present study investigates the control of diastolic [Ca(2+) ]i in rat ventricular myocytes. We show that diastolic [Ca(2+) ]i is increased by manoeuvres that decrease sarcoplasmic reticulum function. This is accompanied by a decrease of systolic [Ca(2+) ]i such that the time-averaged [Ca(2+) ]i remains constant...
June 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28606867/testosterone-deficiency-prevents-left-ventricular-contractility-dysfunction-after-myocardial-infarction
#19
REVIEW
R F Ribeiro Júnior, K S Ronconi, I C G Jesus, P W M Almeida, L Forechi, D V Vassallo, S Guatimosim, I Stefanon, A A Fernandes
Testosterone may affect myocardial contractility since its deficiency decreases the contraction and relaxation of the heart. Meanwhile, testosterone replacement therapy has raised concerns because it may worsen cardiac dysfunction and remodeling after myocardial infarction (MI). In this study, we evaluate cardiac contractility 60 days after MI in rats with suppressed testosterone. Male Wistar rats underwent bilateral orchidectomy one week before the ligation of the anterior descending left coronary artery. The animals were divided into orchidectomized (OCT); MI; orchidectomized + MI (OCT + MI); orchidectomized + MI + testosterone (OCT + MI + T) and control (Sham) groups...
June 9, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28603004/ion-channel-signaling-influences-cellular-proliferation-and-phagocyte-activity-during-axolotl-tail-regeneration
#20
Brandon M Franklin, S Randal Voss, Jeffrey L Osborn
Little is known about the potential for ion channels to regulate cellular behaviors during tissue regeneration. Here, we utilized an amphibian tail regeneration assay coupled with a chemical genetic screen to identify ion channel antagonists that altered critical cellular processes during regeneration. Inhibition of multiple ion channels either partially (anoctamin1/Tmem16a, anoctamin2/Tmem16b, KV2.1, KV2.2, L-type CaV channels and H/K ATPases) or completely (GlyR, GABAAR, KV1.5 and SERCA pumps) inhibited tail regeneration...
August 2017: Mechanisms of Development
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