Medical College of Wisconsin
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Proteostasis and REDOX state in the heart. Am J Physiol Heart Circ Physiol 2012 Jan 01;302(1):H24-37

Date

10/18/2011

Pubmed ID

22003057

Pubmed Central ID

PMC3334238

DOI

10.1152/ajpheart.00903.2011

Scopus ID

2-s2.0-84255167180   49 Citations

Abstract

Force-generating contractile cells of the myocardium must achieve and maintain their primary function as an efficient mechanical pump over the life span of the organism. Because only half of the cardiomyocytes can be replaced during the entire human life span, the maintenance strategy elicited by cardiac cells relies on uninterrupted renewal of their components, including proteins whose specialized functions constitute this complex and sophisticated contractile apparatus. Thus cardiac proteins are continuously synthesized and degraded to ensure proteome homeostasis, also termed "proteostasis." Once synthesized, proteins undergo additional folding, posttranslational modifications, and trafficking and/or become involved in protein-protein or protein-DNA interactions to exert their functions. This includes key transient interactions of cardiac proteins with molecular chaperones, which assist with quality control at multiple levels to prevent misfolding or to facilitate degradation. Importantly, cardiac proteome maintenance depends on the cellular environment and, in particular, the reduction-oxidation (REDOX) state, which is significantly different among cardiac organelles (e.g., mitochondria and endoplasmic reticulum). Taking into account the high metabolic activity for oxygen consumption and ATP production by mitochondria, it is a challenge for cardiac cells to maintain the REDOX state while preventing either excessive oxidative or reductive stress. A perturbed REDOX environment can affect protein handling and conformation (e.g., disulfide bonds), disrupt key structure-function relationships, and trigger a pathogenic cascade of protein aggregation, decreased cell survival, and increased organ dysfunction. This review covers current knowledge regarding the general domain of REDOX state and protein folding, specifically in cardiomyocytes under normal-healthy conditions and during disease states associated with morbidity and mortality in humans.

Author List

Christians ES, Benjamin IJ

Author

Ivor J. Benjamin MD Center Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Heart Diseases
Homeostasis
Humans
Muscle Proteins
Myocardial Contraction
Myocardium
Oxidation-Reduction
Oxidative Stress
Protein Conformation
Protein Folding
Structure-Activity Relationship
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