Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autor principal: Sawicki, Grzegorz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3886579/
https://www.ncbi.nlm.nih.gov/pubmed/24455428
http://dx.doi.org/10.1155/2013/130451
_version_ 1782478899873054720
author Sawicki, Grzegorz
author_facet Sawicki, Grzegorz
author_sort Sawicki, Grzegorz
collection PubMed
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.
format Online
Article
Text
id pubmed-3886579
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Hindawi Publishing Corporation
record_format MEDLINE/PubMed
spelling pubmed-38865792014-01-22 Intracellular Regulation of Matrix Metalloproteinase-2 Activity: New Strategies in Treatment and Protection of Heart Subjected to Oxidative Stress Sawicki, Grzegorz Scientifica (Cairo) Review Article 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. Hindawi Publishing Corporation 2013 2013-12-24 /pmc/articles/PMC3886579/ /pubmed/24455428 http://dx.doi.org/10.1155/2013/130451 Text en Copyright © 2013 Grzegorz Sawicki. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Sawicki, Grzegorz
Intracellular Regulation of Matrix Metalloproteinase-2 Activity: New Strategies in Treatment and Protection of Heart Subjected to Oxidative Stress
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
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3886579/
https://www.ncbi.nlm.nih.gov/pubmed/24455428
http://dx.doi.org/10.1155/2013/130451
work_keys_str_mv AT sawickigrzegorz intracellularregulationofmatrixmetalloproteinase2activitynewstrategiesintreatmentandprotectionofheartsubjectedtooxidativestress