Ethanol Induces CYP2E1 by Protein Stabilization
Open accessAbstract
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.
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Formation of adduct proteins can prolong protein half-lives and accumulate as aggregated proteins; AA adduct formation and ubiquitin conjugation may compete for common lysine residues, so when lysine residues are occupied by reactive acetaldehyde, lipid aldehydes, AGEs, or AA, adducts persist and may aggregate due to lack of free lysine for ubiquitin conjugation and proteolysis.
“The formation of adduct proteins can prolong protein half-lives and accumulate as aggregated proteins.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [186]
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References 24 · Cited by 267
Research works printed but not linked: 2
- Eliasson, E., Johansson, I., and Ingelman-Sundberg, M. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 3225-3229
- Cook, J. C., and Chock, P. B. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 3454 -3457
- Authors
- Roberts, B. J., Song, B.-J., Soh, Y., Park, S. S., & Shoaf, S. E.
- Affiliations
- National Institute on Alcohol Abuse and Alcoholism (US)
- National Institutes of Health (US)
- Corresponding author
- Roberts, Ben J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1995-12
- Volume
- 270
- Issue
- 50
- Pages
- 29632-29635
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1562445183
- Cited by
- 267
- References
- 24
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 7 · 2022: 4 · 2021: 8 · 2020: 4 · 2019: 12 · 2018: 8 · 2017: 6 · 2016: 10 · 2015: 6 · 2014: 10 · 2013: 8 · 2012: 8
- FWCI
- 10.61
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- ethanol, CYP2E1, cytochrome P450 induction, protein stabilization, protein degradation, ubiquitin-proteasome system, ubiquitin conjugates, CYP2B1/2, half-life
- MeSH terms
- Ethanol, Animals, Antibodies, Monoclonal, Cytochrome P-450 Enzyme System, Cytosol, Enzyme Induction, Kinetics, Liver, Male, Microsomes, Liver, Oxidoreductases, N-Demethylating, Reference Values, Time Factors, Ubiquitins, Immunoblotting, Rats, Sprague-Dawley, Cytochrome P-450 CYP2E1, Mice, Rats
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