NDLI: Chronic administration of KB-R7943 induces up-regulation of cardiac NCX1.

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Chronic administration of KB-R7943 induces up-regulation of cardiac NCX1.

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Chronic administration of KB-R7943 induces up-regulation of cardiac NCX1.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Shepherd, Neal R. Renaud, Ludivine Mani, Santhosh K. Conway, Simon J. Xu, Lin Menick, Donald R. Snider, Paige Kappler, Christiana S.
Description	Author Affiliation: Xu L ( Department of Medicine, Gazes Cardiac Research Institute, Division of Cardiology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.)
Abstract	The NCX1 (sodium-calcium exchanger) is up-regulated in human heart failure and in many animal models of heart failure. The potential benefits and risks of therapeutically blocking NCX1 in heart failure and during ischemia-reperfusion are being actively investigated. In this study, we demonstrate that prolonged administration of the NCX1 inhibitor KB-R7943 resulted in the up-regulation of Ncx1 gene expression in both isolated adult cardiomyocytes and intact mouse hearts. Ncx1 up-regulation is mediated by the activation of p38. Importantly, p38 is not activated by KB-R7943 treatment in heart tubes from Ncx1(-/-) mice at 9.5 days postcoitum but is activated in heart tubes from Ncx1(+/+) mice. p38 activation does not appear to be in response to changes in cytosolic calcium concentration, [Ca(2+)](i). Interestingly, chronic KB-R7943 treatment in mice leads to the formation of an NCX1-p38 complex. Our study demonstrates for the first time that the electrogenic sarcolemma membrane cardiac NCX1 can act as a regulator of 'activity-dependent signal transduction' leading to changes in gene expression.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	40
Volume Number	284
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2009-10-02
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Heart Drug Effects Myocardium Metabolism Sodium-Calcium Exchanger Genetics Thiourea Analogs & Derivatives Up-Regulation Adrenergic Beta-Antagonists Administration & Dosage Pharmacology Animals Anti-Arrhythmia Agents Calcium Channel Blockers Calcium Channels, L-Type Enzyme Activation Mice Myocytes, Cardiac Receptors, Adrenergic, Beta Sodium-Hydrogen Antiporter Antagonists & Inhibitors Time Factors P38 Mitogen-Activated Protein Kinases Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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