Cytochrome P-450-mediated differential oxidative modification of proteins: Albumin, apolipoprotein E, and CYP2E1 as targets

Woong Choi Dal, Brigitte Leininger-Muller, Maria Wellman, Hwan Kim Young, Gerard Siest

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2061-2071
Number of pages11
JournalJournal of Toxicology and Environmental Health - Part A
Volume67
Issue number23-24
DOIs
Publication statusPublished - 2004 Dec

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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