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

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 Ca(2+) decay (tau). 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 tau. Interestingly, the malondialdehyde-induced cardiac mechanical effect was abolished by both the p38 MAP kinase inhibitor SB203580 (1 and 10 micro M) and the antioxidant vitamin C (100 micro M). 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.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Folden DV,Gupta A,Sharma AC,Li SY,Saari JT,Ren J

doi

10.1038/sj.bjp.0705384

subject

Has Abstract

pub_date

2003-08-01 00:00:00

pages

1310-6

issue

7

eissn

0007-1188

issn

1476-5381

journal_volume

139

pub_type

杂志文章

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