INDUCTION OF CYP2E1 IN LIVER, KIDNEY, BRAIN AND INTESTINE DURING CHRONIC ETHANOL ADMINISTRATION AND WITHDRAWAL - EVIDENCE THAT CYP2E1 POSSESSES A RAPID PHASE HALFLIFE OF 6 HOURS OR LESS

Controversy exists as to whether the induction of CYP2E1 by ethanol oc curs via increased protein synthesis or protein stabilization. To addr ess these issues in vivo, we chronically administered ethanol to rats and determined levels of immunoreactive CYP2E1 in liver, kidney, brain and upper gastro-intestinal tract (GI). Our data shows that chronic e thanol administration induces hepatic (5-6-foId over pair-fed controls ) and extra-hepatic CYP2E1, an effect which is strikingly absent 12 ho urs after ethanol withdrawal. No changes in CYP2E1 mRNA were observed at any time, suggesting these changes are mainly post-translational at a blood ethanol concentration of 0.15% w/v. Our experimental data ind icates that CYP2E1 possesses a half-life of 6 hours or less in the liv er and is rapidly degraded following the removal of ethanol. This patt ern of CYP2E1 turnover was also observed in other tissues, suggestive of a similar mode of regulation. (C) 1994 Academic Press, Inc.