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https://www.readbyqxmd.com/read/29019935/cardiotoxic-effects-of-short-term-doxorubicin-administration-involvement-of-connexin-43-in-calcium-impairment
#1
Michela Pecoraro, Antonio Rodríguez-Sinovas, Stefania Marzocco, Michele Ciccarelli, Guido Iaccarino, Aldo Pinto, Ada Popolo
The use of Doxorubicin (DOXO), a potent antineoplastic agent, is limited by the development of cardiotoxicity. DOXO-induced cardiotoxicity is multifactorial, although alterations in calcium homeostasis, seem to be involved. Since even the Connexin43 (Cx43) plays a pivotal role in these two phenomena, in this study we have analyzed the effects of DOXO on Cx43 expression and localization. Damage caused by anthracyclines on cardiomyocytes is immediate after each injection, in the present study we used a short-term model of DOXO-induced cardiomyopathy...
October 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28966144/effects-of-exercise-training-on-excitation-contraction-coupling-calcium-dynamics-and-protein-expression-in-the-heart-of-the-neotropical-fish-brycon-amazonicus
#2
Rafael Zanelli Rissoli, Eliton da Silva Vasconcelos, Francisco Tadeu Rantin, Ana Lúcia Kalinin
Matrinxã (Brycon amazonicus) is a great swimming performance teleost fish from the Amazon basin. However, the possible cardiac adaptations of this ability are still unknown. Therefore, the aim of the present work was to investigate the effects of prolonged exercise (EX group - 60days under 0.4BL·s(-1)) on ventricular contractility by (i) in-vitro analysis of contractility comparing the relative roles of sodium/calcium exchanger (NCX) and sarcoplasmic reticulum (SR) in the excitation-contraction (E-C) coupling and (ii) molecular analysis of NCX, sarcoplasmic reticulum Ca(2+) ATPase (SERCA2) and phospholamban (PLB) expression and quantification...
September 29, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28963187/evangelia-kranias-the-mother-of-phospholamban
#3
Susan Ince
No abstract text is available yet for this article.
September 29, 2017: Circulation Research
https://www.readbyqxmd.com/read/28955223/ca-2-calmodulin-dependent-protein-kinase-ii-and-androgen-signaling-pathways-modulate-mef2-activity-in-testosterone-induced-cardiac-myocyte-hypertrophy
#4
Javier Duran, Daniel Lagos, Mario Pavez, Mayarling F Troncoso, Sebastián Ramos, Genaro Barrientos, Cristian Ibarra, Sergio Lavandero, Manuel Estrada
Testosterone is known to induce cardiac hypertrophy through androgen receptor (AR)-dependent and -independent pathways, but the molecular underpinnings of the androgen action remain poorly understood. Previous work has shown that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and myocyte-enhancer factor 2 (MEF2) play key roles in promoting cardiac myocyte growth. In order to gain mechanistic insights into the action of androgens on the heart, we investigated how testosterone affects CaMKII and MEF2 in cardiac myocyte hypertrophy by performing studies on cultured rat cardiac myocytes and hearts obtained from adult male orchiectomized (ORX) rats...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28943852/metabolic-stress-induced-activation-of-ampk-and-inhibition-of-constitutive-phosphoproteins-controlling-smooth-muscle-contraction-evidence-for-smooth-muscle-fatigue
#5
Corey A Smith, Amy S Miner, Robert W Barbee, Paul H Ratz
Metabolic stress diminishes smooth muscle contractile strength by a poorly defined mechanism. To test the hypothesis that metabolic stress activates a compensatory cell signaling program to reversibly downregulate contraction, arterial rings and bladder muscle strips in vitro were deprived of O2 and glucose for 30 and 60 min ("starvation") to induce metabolic stress, and the phosphorylation status of proteins involved in regulation of contraction and metabolic stress were assessed in tissues under basal and stimulated conditions...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28903365/protective-effects-of-circulating-microvesicles-derived-from-myocardial-ischemic-rats-on-apoptosis-of-cardiomyocytes-in-myocardial-ischemia-reperfusion-injury
#6
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...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28887411/age-related-pacemaker-deterioration-is-due-to-impaired-intracellular-and-membrane-mechanisms-insights-from-numerical-modeling
#7
Joachim Behar, Yael Yaniv
Age-related deterioration of pacemaker function has been documented in mammals, including humans. In aged isolated sinoatrial node tissues and cells, reduction in the spontaneous action potential (AP) firing rate was associated with deterioration of intracellular and membrane mechanisms; however, their relative contribution to age-associated deficient pacemaker function is not known. Interestingly, pharmacological interventions that increase posttranslation modification signaling activities can restore the basal and maximal AP firing rate, but the identities of the protein targets responsible for AP firing rate restoration are not known...
September 8, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28878117/tead1-is-required-for-maintaining-adult-cardiomyocyte-function-and-its-loss-results-in-lethal-dilated-cardiomyopathy
#8
Ruya Liu, Jeongkyung Lee, Byung S Kim, Qiongling Wang, Samuel K Buxton, Nikhil Balasubramanyam, Jean J Kim, Jianrong Dong, Aijun Zhang, Shumin Li, Anisha A Gupte, Dale J Hamilton, James F Martin, George G Rodney, Cristian Coarfa, Xander Ht Wehrens, Vijay K Yechoor, Mousumi Moulik
Heart disease remains the leading cause of death worldwide, highlighting a pressing need to identify novel regulators of cardiomyocyte (CM) function that could be therapeutically targeted. The mammalian Hippo/Tead pathway is critical in embryonic cardiac development and perinatal CM proliferation. However, the requirement of Tead1, the transcriptional effector of this pathway, in the adult heart is unknown. Here, we show that tamoxifen-inducible adult CM-specific Tead1 ablation led to lethal acute-onset dilated cardiomyopathy, associated with impairment in excitation-contraction coupling...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28861149/posttranslational-modifications-of-calcium-calmodulin-dependent-protein-kinase-ii%C3%AE-and-its-downstream-signaling-in-human-failing-hearts
#9
Tomas Rajtik, Eva Goncalvesova, Zoltan V Varga, Przemyslaw Leszek, Mariusz Kusmierczyk, Michal Hulman, Jan Kyselovic, Peter Ferdinandy, Adriana Adameova
BACKGROUND: In human failing hearts (HF) of different origin (coronary artery disease-CAD, dilated-DCM, restrictive and hypertrophic cardiomyopathy-OTHER), we investigated the active forms of Ca(2+)/calmodulin-dependent protein kinase IIδ (p-Thr(287)-CaMKIIδ, oxMet(281/282)-CaMKIIδ) and their role in phenotypes of the disease. METHODS AND RESULTS: Although basic diagnostic and clinical markers indicating the attenuated cardiac contractility and remodeling were comparable in HF groups, CaMKIIδ-mediated axis was different...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28859968/dipeptidyl-peptidase-4-independent-cardiac-dysfunction-links-saxagliptin-to-heart-failure
#10
Chintan N Koyani, Ewald Kolesnik, Gerald Wölkart, Niroj Shrestha, Susanne Scheruebel, Christopher Trummer, Klaus Zorn-Pauly, Astrid Hammer, Petra Lang, Helga Reicher, Heinrich Maechler, Klaus Groschner, Bernd Mayer, Peter P Rainer, Harald Sourij, Wolfgang Sattler, Ernst Malle, Brigitte Pelzmann, Dirk von Lewinski
Saxagliptin treatment has been associated with increased rate of hospitalization for heart failure in type 2 diabetic patients, though the underlying mechanism(s) remain elusive. To address this, we assessed the effects of saxagliptin on human atrial trabeculae, guinea pig hearts and cardiomyocytes. We found that the primary target of saxagliptin, dipeptidyl peptidase-4, is absent in cardiomyocytes, yet saxagliptin internalized into cardiomyocytes and impaired cardiac contractility via inhibition of the Ca(2+)/calmodulin-dependent protein kinase II-phospholamban-sarcoplasmic reticulum Ca(2+)-ATPase 2a axis and Na(+)-Ca(2+) exchanger function in Ca(2+) extrusion...
August 30, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28842436/ca-2-calmodulin-kinase-ii-dependent-regulation-of-atrial-myocyte-late-na-current-ca-2-cycling-and-excitability-a-mathematical-modeling-study
#11
Birce Onal, Daniel Gratz, Thomas J Hund
Atrial fibrillation (AF) affects more than 3 million people per year in the U.S., and is associated with high morbidity and mortality. Both electrical and structural remodeling contribute to AF, but the molecular pathways underlying AF pathogenesis are not well understood. Recently, a role for Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in regulation of persistent "late" sodium current (INa,L) has been identified. While INa,L inhibition is emerging as a potential antiarrhythmic strategy in AF patients, little is known about the mechanism linking INa,L to atrial arrhythmogenesis...
August 25, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28759816/phospholamban-immunostaining-is-a-highly-sensitive-and-specific-method-for-diagnosing-phospholamban-p-arg14del-cardiomyopathy
#12
Wouter P Te Rijdt, Z Joy van der Klooster, Edgar T Hoorntje, Jan D H Jongbloed, Paul A van der Zwaag, Folkert W Asselbergs, Dennis Dooijes, Rudolf A de Boer, J Peter van Tintelen, Maarten P van den Berg, Aryan Vink, Albert J H Suurmeijer
Phospholamban (PLN) p.Arg14del cardiomyopathy is associated with an increased risk of malignant ventricular arrhythmias and severe heart failure and a poor prognosis from late adolescence. It can be diagnosed in whole heart specimens, but rarely in right ventricular biopsy specimens, by PLN immunohistochemistry showing PLN-containing aggregates concentrated in cardiomyocytes in dense perinuclear aggresomes. The purpose of this study was to determine whether PLN immunohistochemistry can be used to diagnose PLN p...
September 2017: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/28754591/camkii-inhibition-mitigates-ischemia-reperfusion-elicited-calpain-activation-and-the-damage-to-membrane-skeleton-proteins-in-isolated-rat-hearts
#13
Ling-Heng Kong, Xiao-Ming Gu, Feng Wu, Zhen-Xiao Jin, Jing-Jun Zhou
Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) has been implicated in myocardial ischemia/reperfusion (IR) injury. The aim of this study was to determine the effect of CaMKII on the damage to membrane skeleton proteins, which is an important cause of IR injury. Isolated rat hearts were subjected to 45-min global ischemia/2-h reperfusion. Both KN-62 and KN-93 were used to inhibit CaMKII. Compared with controls, the hearts in the IR group exhibited remarkable myocardial injury area, LDH release, cell apoptosis and contractile dysfunction, along with an increase in the phosphorylation of CaMKII and its substrate phospholamban...
September 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28753475/presenilin-1-mutation-decreases-both-calcium-and-contractile-responses-in-cerebral-arteries
#14
Xavier Toussay, Jean-Luc Morel, Nathalie Biendon, Lolita Rotureau, François-Pierre Legeron, Marie-Charlotte Boutonnet, Yoon H Cho, Nathalie Macrez
Mutations or upregulation in presenilin 1 (PS1) gene are found in familial early-onset Alzheimer's disease or sporadic late-onset Alzheimer's disease, respectively. PS1 has been essentially studied in neurons and its mutation was shown to alter intracellular calcium (Ca(2+)) signals. Here, we showed that PS1 is expressed in smooth muscle cells (SMCs) of mouse cerebral arteries, and we assessed the effects of the deletion of exon 9 of PS1 (PS1dE9) on Ca(2+) signals and contractile responses of vascular SMC. Agonist-induced contraction of cerebral vessels was significantly decreased in PS1dE9 both in vivo and ex vivo...
June 24, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28734932/a-pyridone-derivative-activates-serca2a-by-attenuating-the-inhibitory-effect-of-phospholamban
#15
Manami Kaneko, Hisato Yamamoto, Hiroki Sakai, Yusuke Kamada, Toshiki Tanaka, Shuji Fujiwara, Syunsuke 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...
November 5, 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
#16
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
#17
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
#18
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
#19
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
#20
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
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