Calcium flux balance in the heart

Eisner, David; Bode, Elizabeth; Venetucci, Luigi; Trafford, Andrew W.

doi:10.1016/j.yjmcc.2012.11.017

Cited by 100 publications

(83 citation statements)

References 65 publications

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“…4). Indeed, SR Ca 2 þ content increased following transduction of ILK WT and ILK R211A , in line with the ILK-regulated activation of CaMKII-and ILK-dependent increase in SERCA-2a/PLN function 44 .…”

Section: Resultssupporting

confidence: 57%

Integrin-linked kinase mediates force transduction in cardiomyocytes by modulating SERCA2a/PLN function

Traister

Aafaqi

et al. 2014

Nat Commun

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Human dilated cardiomyopathy (DCM) manifests as a profound reduction in biventricular cardiac function that typically progresses to death or cardiac transplantation. There is no effective mechanism-based therapy currently available for DCM, in part because the transduction of mechanical load into dynamic changes in cardiac contractility (termed mechanotransduction) remains an incompletely understood process during both normal cardiac function and in disease states. Here we show that the mechanoreceptor protein integrin-linked kinase (ILK) mediates cardiomyocyte force transduction through regulation of the key calcium regulatory protein sarcoplasmic/endoplasmic reticulum Ca 2 þ ATPase isoform 2a (SERCA-2a) and phosphorylation of phospholamban (PLN) in the human heart. A non-oncogenic ILK mutation with a synthetic point mutation in the pleckstrin homology-like domain (ILK R211A ) is shown to enhance global cardiac function through SERCA-2a/PLN. Thus, ILK serves to link mechanoreception to the dynamic modulation of cardiac contractility through a previously undiscovered interaction with the functional SERCA-2a/PLN module that can be exploited to rescue impaired mechanotransduction in DCM.

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Section: Resultssupporting

confidence: 57%

Integrin-linked kinase mediates force transduction in cardiomyocytes by modulating SERCA2a/PLN function

Traister

Aafaqi

et al. 2014

Nat Commun

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“…The expression and activity of sarcoplasmic reticulum Ca 2+ -ATPase (SERCA2a) is the main factor involved in calcium handling, as its dysfunction impairs myocardial systolic/diastolic function [10]. Phospholamban (PLB), a phosphoprotein that is mainly expressed in ventricular myocytes, is tightly related to SERCA2a activity; thus, it indirectly regulates the sarcoplasmic reticulum (SR) absorption of calcium during diastole [11, 12]. In its dephosphorylated state, PLB inhibits SERCA2a function, leading to reduced Ca 2+ re-uptake into the SR and cardiac contractility.…”

Section: Introductionmentioning

confidence: 99%

Luteolin Enhances Sarcoplasmic Reticulum Ca2+-ATPase Activity through p38 MAPK Signaling thus Improving Rat Cardiac Function after Ischemia/Reperfusion

Zhu

Luo

et al. 2017

Cell Physiol Biochem

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Background/Aims: A major challenge for current therapeutic strategies against ischemia/reperfusion (I/R) is the lack of effective drugs. Considering luteolin enhances the activity of sarcoplasmic reticulum Ca²⁺-ATPase (SERCA2a) to improve the systolic/diastolic function of rat hearts and cardiomyocytes during the I/R process, we studied the regulatory function of the p38 MAPK pathway in this protective mechanism. Methods: Isolated cardiomyocytes and perfused hearts were separately divided into five groups and used to investigate I/R. The phosphorylation of p38 and phospholamban (p-PLB), the levels and activity of SERCA2a and the levels of proteins related to apoptosis were measured. Apoptotic cells were assessed using the TUNEL assay. Single-cell shortening, Ca²⁺ transients, and the decay of the mitochondrial membrane potential (Δψm) were detected. Results: The p38 MAPK pathway was activated during the I/R process, and inhibiting it with SB203580 promoted p-PLB, which enhanced the activity of SERCA2a and relieved the calcium overload to promote the recovery of the Δψm and reduce cardiomyocyte apoptosis in I/R. Luteolin also suppressed the activation of the p38 MAPK pathway and showed cardioprotective effects during I/R injury. Conclusions: We conclude that luteolin enhances SERCA2a activity to improve systolic/diastolic function during I/R in rat hearts and cardiomyocytes by attenuating the inhibitive effects of the p38 pathway on p-PLB.

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“…Intracellular Ca 2+ handling is a critical regulator of action potential duration, and mechanical activity of cardiomyocytes via excitation‐contraction coupling 9. Abnormalities in its homeostasis can therefore reduce cardiac output and potentially leading to mortality but also initiate arrhythmogenic triggers in the atrial or ventricular myocardium 10, 11, 12. Previous studies have reported that XO inhibition has beneficial effects on cardiac remodeling,13, 14, 15 mechano‐energetics16 and endothelial function17 both in experimental and clinical studies.…”

mentioning

confidence: 99%

Xanthine Oxidase Inhibitor Allopurinol Prevents Oxidative Stress‐Mediated Atrial Remodeling in Alloxan‐Induced Diabetes Mellitus Rabbits

Yang

Zhao

Qiu

et al. 2018

JAHA

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BackgroundThere are several mechanisms, including inflammation, oxidative stress and abnormal calcium homeostasis, involved in the pathogenesis of atrial fibrillation. In diabetes mellitus (DM), increased oxidative stress may be attributable to higher xanthine oxidase activity. In this study, we examined the relationship between oxidative stress and atrial electrical and structural remodeling, and calcium handling abnormalities, and the potential beneficial effects of the xanthine oxidase inhibitor allopurinol upon these pathological changes.Methods and ResultsNinety rabbits were randomly and equally divided into 3 groups: control, DM, and allopurinol‐treated DM group. Echocardiographic and hemodynamic assessments were performed in vivo. Serum and tissue markers of oxidative stress and atrial fibrosis, including the protein expression were examined. Atrial interstitial fibrosis was evaluated by Masson trichrome staining. ICaL was measured from isolated left atrial cardiomyocytes using voltage‐clamp techniques. Confocal microscopy was used to detect intracellular calcium transients. The Ca2+ handling protein expression was analyzed by Western blotting. Mitochondrial‐related proteins were analyzed as markers of mitochondrial function. Compared with the control group, rabbits with DM showed left ventricular hypertrophy, increased atrial interstitial fibrosis, oxidative stress and fibrosis markers, ICaL and intracellular calcium transient, and atrial fibrillation inducibility. These abnormalities were alleviated by allopurinol treatment.ConclusionsAllopurinol, via its antioxidant effects, reduces atrial mechanical, structural, ion channel remodeling and mitochondrial synthesis abnormalities induced by DM‐related increases in oxidative stress.

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Calcium flux balance in the heart

Cited by 100 publications

References 65 publications

Integrin-linked kinase mediates force transduction in cardiomyocytes by modulating SERCA2a/PLN function

Integrin-linked kinase mediates force transduction in cardiomyocytes by modulating SERCA2a/PLN function

Luteolin Enhances Sarcoplasmic Reticulum Ca2+-ATPase Activity through p38 MAPK Signaling thus Improving Rat Cardiac Function after Ischemia/Reperfusion

Xanthine Oxidase Inhibitor Allopurinol Prevents Oxidative Stress‐Mediated Atrial Remodeling in Alloxan‐Induced Diabetes Mellitus Rabbits

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