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]

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