Expression of constitutive and inducible cytochrome P450 2E1 in rat brain
Abstract
Studies initiated to investigate the expression of cytochrome P450 2E1 (CYP2E1) in rat brain demonstrated low but detectable protein and mRNA expression in control rat brain. Though mRNA and protein expression of CYP2E1 in brain was several fold lower as compared to liver, relatively high activity of N-nitrosodimethylamine demethylase (NDMA-d) was observed in control rat brain microsomes. Like liver, pretreatment with CYP2E1 inducers such as ethanol or pyrazole or acetone significantly increased the activity of brain microsomal NDMA-d. Kinetic studies also showed an increase in the Vmax and affinity (Km) of the substrate towards the brain enzyme due to increased expression of CYP2E1 in microsomes of brain isolated from ethanol pretreated rats. In vitro studies using organic inhibitors, specific for CYP2E1 and anti-CYP2E1 significantly inhibited the brain NDMA-d activity indicating that like liver, NDMA-d activity in rat brain is catalyzed by CYP2E1. Olfactory lobes exhibited the highest CYP2E1 expression and catalytic activity in control rats. Furthermore, several fold increase in the mRNA expression and activity of CYP2E1 in cerebellum and hippocampus while a relatively small increase in the olfactory lobes and no significant change in other brain regions following ethanol pretreatment have indicated that CYP2E1 induction maybe involved in selective sensitivity of these brain areas to ethanol induced free radical damage and neuronal degeneration.
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CYP2E1 is widely expressed throughout the brain, such as in the cerebral cortex, hippocampus, and cerebellum; brain CYP2E1 is inducible by ethanol and may play a key role in cerebral ethanol metabolism, especially after chronic and/or binge alcohol intake.
“In contrast, CYP2E1 is widely expressed throughout the brain, such as in the cerebral cortex, hippocampus, and cerebellum.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [152]
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- Authors
- Yadav, S., Dhawan, A., Singh, R. L., Seth, P. K., & Parmar, D.
- Affiliations
- Indian Institute of Toxicology Research (IN)
- Dr. Ram Manohar Lohia Avadh University (IN)
- Corresponding author
- Parmar, Devendra
- Venue
- Molecular and Cellular Biochemistry
- Published
- 2006-04-21
- Volume
- 286
- Issue
- 1-2
- Pages
- 171-180
- ISSN
- 0300-8177 (ISSN-L)
- 1573-4919
- OpenAlex
- W1972609199
- Cited by
- 45
- References
- 44
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2022: 1 · 2021: 2 · 2019: 4 · 2017: 3 · 2016: 3 · 2015: 2 · 2014: 3 · 2013: 4 · 2012: 1
- FWCI
- 4.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Molecular and Cellular Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Iran Telecommunication Research Center
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- CYP2E1, brain microsomes, ethanol induction, pyrazole derivatives, acetone, olfactory lobe, cerebellum, hippocampus, oxidative damage, neurodegeneration, rat brain
- MeSH terms
- Acetone, Ethanol, Animals, Brain, Central Nervous System Depressants, Enzyme Inhibitors, Kinetics, Liver, Male, Microsomes, Pyrazoles, RNA, Messenger, Blotting, Western, Gene Expression Regulation, Enzymologic, Cytochrome P-450 CYP2E1, Reverse Transcriptase Polymerase Chain Reaction, Rats, Cytochrome P-450 CYP2E1 Inhibitors
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