Cytochrome p-450-mediated differential oxidative modification of proteins: albumin, apolipoprotein E, and CYP2E1 as targets.
Although many studies established a role of cytochrome P-450s in metabolism of xenobiotics, few studies evaluating the ability of cytochrome P-450s to oxidize proteins have been reported. The ability of cytochrome P-450s to induce oxidative modification of albumin, apolipoprotein E, and CYP2E1 protein was investigated. Microsomal cytochrome P-450s induced production of reactive radical species, leading to differential modification of the proteins. Albumin remained unmodified, and CYP2E1 protein was degraded, whereas recombinant and endogenous apolipoprotein E was aggregated. The modification of apolipoprotein E was isoform independent. Cytochrome P-450 inhibitors or antioxidants inhibited the production of reactive radical species and protein modification. These results demonstrate that response of each protein to cytochrome P-450-mediated oxidative attack is different, and cytochrome P-450s can induce apolipoprotein E aggregation, a process that might be relevant to accumulation of altered protein in various abnormal conditions. In view of the ubiquitous expression of cytochrome P-450s, the present results may have important toxicological implications.
Choi
Dal Woong
DW
INSERM U525, Faculté de Pharmacie, Université Nancy, Nancy, France.
Leininger-Muller
Brigitte
B
Wellman
Maria
M
Kim
Young Hwan
YH
Siest
Gerard
G
D000418:Albumins / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000494:pharmacology*; D004926:Escherichia coli; D007527:Isoenzymes; D008297:Male; D008861:Microsomes; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D015262:Xenobiotics / Q000378:metabolism*
D000418:Albumins; D001057:Apolipoproteins E; D007527:Isoenzymes; D017382:Reactive Oxygen Species; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1