Cytochrome P450: major player in reperfusion injury.
While attention has historically focused on mitochondria as the primary source of ROS in myocardial ischemia/reperfusion injury, recent evidence has implicated cytochrome P450 monooxygenases (CYPs) as a significant factor. CYPs represent a large family of enzymes that catalyze the oxidation of endogenous and exogenous compounds. They catalyze arachidonic acid oxidation to a variety of biologically active eicosanoids that regulate ion channels and protein kinases, with effects on vasomotor tone and cardiac inotropy. They also represent a significant source of reactive oxygen species that may target cellular homeostatic mechanisms and mitochondria. In this review, we will consider the contribution of cytochrome P450 enzymes to reperfusion injury and will speculate on whether the mechanism of injury is due to CYP-mediated ROS production or arachidonic acid metabolites.
Gottlieb
Roberta A
RA
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 N. Torrey Pines Road MEM220, La Jolla, CA 92037, USA. robbieg@scripps.edu
D000818:Animals; D017209:Apoptosis; D016718:Arachidonic Acid / Q000378:metabolism; D002317:Cardiovascular Agents / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D015777:Eicosanoids / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D007527:Isoenzymes; D017202:Myocardial Ischemia / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology; D017382:Reactive Oxygen Species / Q000378:metabolism
D002317:Cardiovascular Agents; D015777:Eicosanoids; D007527:Isoenzymes; D017382:Reactive Oxygen Species; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System