Cytochrome P-450 2E1 in rat liver peroxisomes: downregulation by ischemia/reperfusion-induced oxidative stress

Free Radic Biol Med. 1997;23(7):963-71. doi: 10.1016/s0891-5849(97)00017-8.


Cytochrome P-450 containing enzymes, known to be present in the endoplasmic reticulum and mitochondria, catalyze the oxidation of various compounds. In this study we have used highly purified peroxisomes (> 95%) to provide evidence by analytical cell fractionation, enzyme activity, Western blot, and immunocytochemical analysis that cytochrome P-450 2E1 (Cyp 2E1) is present in peroxisomes. Similar specific activities of aniline hydroxylase, a Cyp 2E1-dependent enzyme, in purified peroxisomes (0.72 +/- 0.03 nmol/min/mg protein) and microsomes (0.58 +/- 0.03 nmol/min/mg protein) supports the conclusion that peroxisomes contain significant amount of Cyp 2E1. This peroxisomal Cyp 2E1 was also induced in acetone-treated rat liver. The status of microsomal and peroxisomal Cyp 2E1 was also examined following ischemia/reperfusion-induced oxidative stress. Ischemia alone had no effect; however, reperfusion following ischemia resulted in decrease in Cyp 2E1 both in microsomes and peroxisomes. This demonstration of cytochrome P-450 2E1 in peroxisomes and its downregulation during ischemia/reperfusion describes a new role for this organelle in cytochrome P-450 related cellular metabolism and in oxidative stress induced disease conditions.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aniline Compounds / metabolism
  • Animals
  • Blotting, Western
  • Cytochrome P-450 CYP2E1 / metabolism*
  • Down-Regulation
  • Hydroxylation
  • Liver / blood supply
  • Liver / enzymology*
  • Male
  • Microbodies / metabolism*
  • NADPH-Ferrihemoprotein Reductase / metabolism
  • Organelles
  • Oxidative Stress / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / metabolism*
  • Subcellular Fractions / metabolism


  • Aniline Compounds
  • Cytochrome P-450 CYP2E1
  • NADPH-Ferrihemoprotein Reductase
  • aniline