Intracellular Regulation of Matrix Metalloproteinase-2 Activity: New Strategies in Treatment and Protection of Heart Subjected to Oxidative Stress

Much is known regarding cardiac energy metabolism in ischemia/reperfusion (I/R) injury. Under aerobic conditions, the heart prefers to metabolize fatty acids, which contribute to 60–80% of the required ATP. During ischemia, anaerobic glycolysis increases and becomes an important source of ATP for pr...

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Main Author: Grzegorz Sawicki
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Scientifica
Online Access:http://dx.doi.org/10.1155/2013/130451
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author Grzegorz Sawicki
author_facet Grzegorz Sawicki
author_sort Grzegorz Sawicki
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description Much is known regarding cardiac energy metabolism in ischemia/reperfusion (I/R) injury. Under aerobic conditions, the heart prefers to metabolize fatty acids, which contribute to 60–80% of the required ATP. During ischemia, anaerobic glycolysis increases and becomes an important source of ATP for preservation of ion gradients. With reperfusion, fatty acid oxidation quickly recovers and again predominates as the major source of mitochondrial oxidative metabolism. Although a number of molecular mechanisms have been implicated in the development of I/R injury, their relative contributions remain to be determined. One such mechanism involves the proteolytic degradation of contractile proteins, such as troponin I (TnI), myosin heavy chain, titin, and the myosin light chains (MLC1 and MLC2) by matrix metalloproteinase-2 (MMP-2). However, very little is known about intracellular regulation of MMP-2 activity under physiological and pathological conditions. Greater understanding of the mechanisms that govern MMP-2 activity may lead to the development of new therapeutic strategies aimed at preservation of the contractile function of the heart subjected to myocardial infarction (MI) or I/R. This review discusses the intracellular mechanisms controlling MMP-2 activity and highlights a new intracellular therapeutic direction for the prevention and treatment of heart injury.
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spelling doaj-art-eb5c5031b88e4fb787aeb6954dd4c3462025-08-20T03:21:16ZengWileyScientifica2090-908X2013-01-01201310.1155/2013/130451130451Intracellular Regulation of Matrix Metalloproteinase-2 Activity: New Strategies in Treatment and Protection of Heart Subjected to Oxidative StressGrzegorz Sawicki0Department of Pharmacology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK, S7N 5E5, CanadaMuch is known regarding cardiac energy metabolism in ischemia/reperfusion (I/R) injury. Under aerobic conditions, the heart prefers to metabolize fatty acids, which contribute to 60–80% of the required ATP. During ischemia, anaerobic glycolysis increases and becomes an important source of ATP for preservation of ion gradients. With reperfusion, fatty acid oxidation quickly recovers and again predominates as the major source of mitochondrial oxidative metabolism. Although a number of molecular mechanisms have been implicated in the development of I/R injury, their relative contributions remain to be determined. One such mechanism involves the proteolytic degradation of contractile proteins, such as troponin I (TnI), myosin heavy chain, titin, and the myosin light chains (MLC1 and MLC2) by matrix metalloproteinase-2 (MMP-2). However, very little is known about intracellular regulation of MMP-2 activity under physiological and pathological conditions. Greater understanding of the mechanisms that govern MMP-2 activity may lead to the development of new therapeutic strategies aimed at preservation of the contractile function of the heart subjected to myocardial infarction (MI) or I/R. This review discusses the intracellular mechanisms controlling MMP-2 activity and highlights a new intracellular therapeutic direction for the prevention and treatment of heart injury.http://dx.doi.org/10.1155/2013/130451
spellingShingle Grzegorz Sawicki
Intracellular Regulation of Matrix Metalloproteinase-2 Activity: New Strategies in Treatment and Protection of Heart Subjected to Oxidative Stress
Scientifica
title Intracellular Regulation of Matrix Metalloproteinase-2 Activity: New Strategies in Treatment and Protection of Heart Subjected to Oxidative Stress
title_full Intracellular Regulation of Matrix Metalloproteinase-2 Activity: New Strategies in Treatment and Protection of Heart Subjected to Oxidative Stress
title_fullStr Intracellular Regulation of Matrix Metalloproteinase-2 Activity: New Strategies in Treatment and Protection of Heart Subjected to Oxidative Stress
title_full_unstemmed Intracellular Regulation of Matrix Metalloproteinase-2 Activity: New Strategies in Treatment and Protection of Heart Subjected to Oxidative Stress
title_short Intracellular Regulation of Matrix Metalloproteinase-2 Activity: New Strategies in Treatment and Protection of Heart Subjected to Oxidative Stress
title_sort intracellular regulation of matrix metalloproteinase 2 activity new strategies in treatment and protection of heart subjected to oxidative stress
url http://dx.doi.org/10.1155/2013/130451
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