The ubiquitin-proteasome system in myocardial ischaemia and preconditioning.
The ubiquitin-proteasome system (UPS) represents the major pathway for degradation of intracellular proteins. This article reviews the major components and configurations of the UPS including the 26S proteasome and 11S activated proteasome relevant to myocardial ischaemia. We then present the evidence that the UPS is dysfunctional during myocardial ischaemia as well as potential consequences of this, including dysregulation of target substrates, many of them active signalling proteins, and accumulation of oxidized proteins. As part of this discussion, potential mechanisms, including ATP depletion, inhibition by insoluble protein aggregates, and oxidation of proteasome and regulatory particle subunits, are discussed. Finally, the evidence suggesting a role for the UPS in ischaemic preconditioning is presented. Much of this is inferential but clearly indicates the need for additional research.
The Cardiac Metabolism Laboratory, The Feinstein Institute for Medical Research, Long Island Jewish Medical Center, 270-05 76th Avenue, Suite B-387, New Hyde Park, NY 11042, USA. spowell@lij.edu
Saul R
SR
Powell
Andras
A
Divald
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000209:etiology*; D015425:Myocardial Reperfusion; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000502:physiology*; D061988:Proteasome Inhibitors; D011506:Proteins / Q000737:chemistry; D025801:Ubiquitin / Q000378:metabolism*
D061988:Proteasome Inhibitors; D011506:Proteins; D025801:Ubiquitin; D000255:Adenosine Triphosphate; D046988:Proteasome Endopeptidase Complex