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

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

Research output: Contribution to journalArticle

6 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 1

Fingerprint

Cytochrome P-450 CYP2E1
Apolipoproteins E
Cytochrome P-450 Enzyme System
Cytochromes
cytochrome
Albumins
Proteins
protein
Xenobiotics
Apolipoproteins
Metabolism
Toxicology
xenobiotics
Protein Isoforms
antioxidant
Agglomeration
Antioxidants
inhibitor
metabolism

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Public Health, Environmental and Occupational Health
  • Pollution
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Cytochrome P-450-mediated differential oxidative modification of proteins : Albumin, apolipoprotein E, and CYP2E1 as targets. / Choi, DalWoong; Leininger-Muller, Brigitte; Wellman, Maria; Young, Hwan Kim; Siest, Gerard.

In: Journal of Toxicology and Environmental Health - Part A, Vol. 67, No. 23-24, 01.12.2004, p. 2061-2071.

Research output: Contribution to journalArticle

Choi, DalWoong ; Leininger-Muller, Brigitte ; Wellman, Maria ; Young, Hwan Kim ; Siest, Gerard. / Cytochrome P-450-mediated differential oxidative modification of proteins : Albumin, apolipoprotein E, and CYP2E1 as targets. In: Journal of Toxicology and Environmental Health - Part A. 2004 ; Vol. 67, No. 23-24. pp. 2061-2071.
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