Matrix metalloproteinase-2 degrades the cytoskeletal protein alpha-actinin in peroxynitrite mediated myocardial injury.

Matrix metalloproteinase-2 degrades the cytoskeletal protein alpha-actinin in peroxynitrite mediated myocardial injury. Research Abstract Details 

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Matrix metalloproteinase-2 degrades the cytoskeletal protein alpha-actinin in peroxynitrite mediated myocardial injury. Abstract Text:

Miranda M Sung,Christina G Schulz,Wenjie Wang,Grzegorz Sawicki,Norma L ,Richard Schulz,Miranda M Sung,Christina G Schulz,Wenjie Wang,Grzegorz Sawicki,Norma L ,Richard Schulz,

Matrix metalloproteinase (MMP)-2 mediates myocardial ischemia-reperfusion injury which is characterized by enhanced peroxynitrite biosynthesis during early reperfusion. Direct infusion of peroxynitrite into isolated hearts activates MMP-2 prior to the loss in mechanical function. The mechanical dysfunction is prevented by MMPs inhibitors. MMP-2 is also found in the sarcomere of cardiomyocytes where it cleaves troponin I and myosin light chain I. Cytoskeletal proteins such as alpha-actinin, desmin and spectrin are found in close association with the sarcomere and are known to be degraded in ischemia-reperfusion injury. It remains unknown whether these proteins are degraded in peroxynitrite-induced myocardial injury and if cytoskeletal proteins are also targets for MMP-2. Peroxynitrite (80 microM) was infused into isolated rat hearts which led to a delayed onset but rapidly developing decline in mechanical function. The MMPs inhibitor PD-166793 or the peroxynitrite scavenger glutathione prevented the decline in cardiac function. At the end of perfusion, alpha-actinin levels were decreased by 45+/-3% in peroxynitrite-infused hearts as compared to control hearts; however, this was normalized to that of control hearts with either PD-166793 or glutathione. Cardiac desmin and alphaII spectrin levels were unaltered following peroxynitrite infusion. alpha-Actinin and to a lesser extent desmin are susceptible to in vitro proteolysis by MMP-2 whereas spectrin is resistant. Cardiac dysfunction induced by peroxynitrite involves degradation of alpha-actinin that may be mediated by the proteolytic action of MMP-2.

Matrix metalloproteinase-2 degrades the cytoskeletal protein alpha-actinin in peroxynitrite mediated myocardial injury. Publishing Authors By Initials

MM Sung,CG Schulz,W Wang,G Sawicki,NL ,R Schulz,MM Sung,CG Schulz,W Wang,G Sawicki,NL ,R Schulz,

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Matrix metalloproteinase-2 degrades the cytoskeletal protein alpha-actinin in peroxynitrite mediated myocardial injury. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of molecular and cellular cardiology

VOLUME: 43

Page Numbers: 429-36

Journal Abbreviation: J. Mol. Cell. Cardiol.

ISSN: 0022-2828

DAY: 31

MONTH: 07

YEAR: 2007

Matrix metalloproteinase-2 degrades the cytoskeletal protein alpha-actinin in peroxynitrite mediated myocardial injury. Information

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LANGUAGE: eng

NlmUniqueID: 262322

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Grant and Affiliation Information for Matrix metalloproteinase-2 degrades the cytoskeletal protein alpha-actinin in peroxynitrite mediated myocardial injury.

AFFILIATION: Department of Pharmacology, Cardiovascular Research Group, 4-62 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.

Country: England

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MEDLINETA: J Mol Cell Cardiol

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