Role of reversible, thioredoxin-sensitive oxidative protein modifications in cardiac myocytes.
Reactive oxygen species (ROS) are important mediators of myocardial remodeling. However, the precise molecular mechanisms by which ROS exert their effects are incompletely understood. ROS induce oxidative posttranslational protein modifications that can regulate the function of structural, functional, and signaling proteins. For example, oxidative modification of free reactive thiols (S-thiolation) on the small G protein Ras increases Ras activity and thereby promotes ROS-dependent hypertrophic signaling in cardiac myocytes. By reducing thiols and restoring reversible thiol modifications, thioredoxin and glutaredoxin can act as regulators of ROS-mediated protein function. Understanding the regulation and functional relevance of oxidative protein modifications in myocardial remodeling may lead to new therapeutic strategies.
Kuster
Gabriela M
GM
Cardiovascular Medicine Section and the Myocardial Biology Unit, Boston University Medical Center, Boston, Massachusetts 02118, USA.
Siwik
Deborah A
DA
Pimentel
David R
DR
Colucci
Wilson S
WS
D000818:Animals; D054477:Glutaredoxins; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013879:Thioredoxins / Q000494:pharmacology*
D054477:Glutaredoxins; D017382:Reactive Oxygen Species; D013879:Thioredoxins; D010088:Oxidoreductases; D020559:Monomeric GTP-Binding Proteins