Induction of CYP2E1 in Liver, Kidney, Brain and Intestine During Chronic Ethanol Administration and Withdrawal: Evidence That CYP2E1 Possesses a Rapid Phase Half-Life of 6 Hours or Less
Abstract
Controversy exists as to whether the induction of CYP2E1 by ethanol occurs via increased protein synthesis or protein stabilization. To address 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 ethanol administration induces hepatic (5-6-fold over pair-fed controls) and extra-hepatic CYP2E1, an effect which is strikingly absent 12 hours 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 indicates that CYP2E1 possesses a half-life of 6 hours or less in the liver and is rapidly degraded following the removal of ethanol. This pattern of CYP2E1 turnover was also observed in other tissues, suggestive of a similar mode of regulation.
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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 [184]
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“Other studies support the ®ndings of this report that ethanol does not induce only CYP2E1 (Roberts et al. 1994).”
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“Cytochrome P450 2E1 (CYP2E1) is a monooxygenase enzyme that is expressed at high levels in liver hepatocytes and is also expressed in many other tissues including kidneys, lung, heart, and brain (Miller, 2008; Roberts et al., 1994; Yadav et al., 2006).”
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- Authors
- Roberts, B. J., Shoaf, S. E., Jeong, K. S., & Song, B. J.
- Affiliations
- National Institute on Alcohol Abuse and Alcoholism (US)
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 1994-12
- Volume
- 205
- Issue
- 2
- Pages
- 1064-1071
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2140725636
- Cited by
- 116
- References
- 0
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 4 · 2022: 1 · 2021: 4 · 2020: 1 · 2019: 7 · 2018: 1 · 2017: 4 · 2016: 1 · 2015: 4 · 2014: 3 · 2013: 4 · 2012: 2
- FWCI
- 4.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- 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
- CYP2E1, chronic ethanol exposure, ethanol withdrawal, enzyme induction, protein stabilization, protein synthesis, protein turnover, half-life, liver, kidney, brain, intestine, blood alcohol concentration
- MeSH terms
- Acetone, Activity Cycles, Alcoholism, Animals, Brain, Cytochrome P-450 Enzyme System, Enzyme Induction, Half-Life, Intestine, Small, Kidney, Male, Microsomes, Microsomes, Liver, Oxidoreductases, N-Demethylating, RNA, Messenger, Substance Withdrawal Syndrome, Blotting, Northern, Rats, Sprague-Dawley, Cytochrome P-450 CYP2E1, Rats
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