1: Life Sci. 2006 Oct 12;79(20):1913-20. Epub 2006 Aug 14. Ageing is associated with increased expression but decreased activity of CYP2E1 in male Wistar rats. Wauthier V, Schenten V, Verbeeck RK, Calderon PB. Unite de Pharmacocinetique, Metabolisme, Nutrition et Toxicologie (PMNT), Departement des sciences pharmaceutiques, Universite Catholique de Louvain, Avenue E. Mounier 73, 1200, Brussels, Belgium. The effect of ageing on CYP2E1 activity and its protein and mRNA contents was investigated in both adult (9 months) and senescent (24 months) male Wistar rats. The CYP2E1 activity (as measured by chlorzoxazone hydroxylation) was significantly decreased by 36% in senescent rats as compared to adult rats. However, this decrease of activity was not associated with a loss of protein content because the amount of both CYP2E1 protein and CYP2E1 mRNA did not decrease in senescent rats but rather increased, by 79% and 64% respectively, as compared to adult rats. Lipid peroxidation was increased significantly by 140% with ageing. The decrease in CYP2E1 activity could be explained by post-translational modification of CYP2E1 proteins, due to an increase in oxidative stress in senescent animals, leading to a loss of their functionality. However, no changes in the extent of protein carbonyls were observed in the adult versus senescent rats (16.2 +/- 9.6 vs. 12.7 +/- 7.3 nmol/mg prot) and the major proteasome activity remained unchanged. With regards to the increase of CYP2E1 expression, our results showed that the amount of hepatocyte nuclear factor 1alpha mRNA, a transcription factor that positively regulates CYP2E1, was strongly increased (154%) in senescent rats. PMID: 16904701 [PubMed - indexed for MEDLINE] Related Links Age-related changes in the protein and mRNA levels of CYP2E1 and CYP3A isoforms as well as in their hepatic activities in Wistar rats. What role for oxidative stress? [Arch Toxicol. 2004] PMID:14600803 CYP2E1 regulation by benzene and other small organic chemicals in rat liver and peripheral lymphocytes. [Toxicol Lett. 2003] PMID:12919724 The effect of endotoxin on hepatocyte nuclear factor 1 nuclear protein binding: potential implications on CYP2E1 expression in the rat. [J Pharm Pharmacol. 2001] PMID:11697544 Decreased CYP3A2 expression and activity in senescent male Wistar rats: is there a role for HNF4alpha? [Exp Gerontol. 2006] PMID:16891075 Effect of methacrylonitrile on cytochrome P-450 2E1 (CYP2E1) expression in male F344 rats. [J Toxicol Environ Health A. 2002] PMID:11939710