Malondialdehyde inhibits cardiac contractile function in ventricular myocytes via a p38 mitogen-activated protein kinase-dependent mechanism

Document Type

Article

Publication Date

2003

Abstract

1. Increased oxidative stress plays a significant role in the etiology of cardiovascular disease. Lipid peroxidation, initiated in the presence of hydroxy radicals resulting in the production of malondialdehyde, directly produces oxidative stress. This study was designed to examine the direct impact of malondialdehyde on ventricular contractile function at the single cardiac myocyte level. Ventricular myocytes from adult rat hearts were stimulated to contract at 0.5 Hz, and mechanical and intracellular Ca 2+ properties were evaluated using an IonOptix Myocam™ system. Contractile properties analyzed included peak shortening amplitude (PS), time-to-PS (TPS), time-to-90% relengthening (TR 90), maximal velocity of shortening/relengthening (±dLdt), and Ca 2+-induced intracellular Ca 2+ fluorescence release (CICR) and intracellular Ca2+ decay. p38 mitogen-activated protein (MAP) kinase phosphorylation was assessed with Western blot. 2. Our results indicated that malondialdehyde directly depressed PS, ±dLdt and CICR in a concentration-dependent manner and shortened TPS without affecting TR 90 and T. Interestingly, the malondialdehyde-induced cardiac mechanical effect was abolished by both the p38 MAP kinase inhibitor SB203580 (1 and 10 µM) and the antioxidant vitamin C (100 µM). Western blot analysis confirmed direct phosphorylation of p38 MAP kinase by malondialdehyde. 3. These findings revealed a novel role of malondialdehyde and p38 MAP kinase in lipid peroxidation and oxidative stress-associated cardiac dysfunction.

Publication Title

British journal of pharmacology

Volume

139

Issue

7

First Page

1310

Last Page

1316

Comments

This article was published in British journal of pharmacology, Volume 139, Issue 7, Pages 1310-1316.

The published version is available at http://dx.doi.org/10.1038/sj.bjp.0705384.

Copyright © 2003 BJP.

This document is currently not available here.

COinS