Work

Ethanol Induces CYP2E1 by Protein Stabilization

Year: 1995

Type: article

Abstract: In the present study, we demonstrate that ethanol induces CYP2E1 by protein stabilization in vivo. The control half-life of CYP2E1 was determined to be 6-7 h followed by a slower secondary phase. The half-life of ethanol-stabilized CYP2E1 was calculated to be 38 h. The mechanism underlying the rapid degradation of CYP2E1 was also investigated and appears to involve the ubiquitin-proteasome proteolytic pathway. An in vitro assay using the cytosolic fraction was developed to further characterize CYP2E1 degradation. Using this assay, 40-50% loss of CYP2E1 was observed in 1 h, coincident with the formation of high M(r) ubiquitin-CYP2E1 conjugates. At concentrations approximating those found in vivo, ethanol protects CYP2E1 from cytosolic degradation. No loss of CYP2B1/2 was observed under identical conditions, suggesting that this reaction is specific for certain P-450s which are rapidly turned over.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.270.50.29632

Authors: Ben J. Roberts, Byoung-Joon Song, Yunjo Soh, Sang S. Park, Susan E. Shoaf

Institutions: National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, National Cancer Institute

Language: English

Topic: Pharmacogenetics and Drug Metabolism

Subfield: Pharmacology

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,430