Ethanol Increases Cytochrome P4502E1 and Induces Oxidative Stress in Astrocytes
Abstract
Abstract: We demonstrate the presence of cytochrome P4502E1 (CYP2E1) in astrocytes in primary culture, its induction by ethanol, and the concomitant generation of free radical species. Double immunofluorescence using anti‐CYP2E1 and anti‐glial fibrillary acidic protein showed that CYP2E1 was distributed over the cytoplasm and processes, although labeling was more pronounced over the nuclear membrane. Immunogold labeling confirmed this pattern of distribution. Addition of 25 m M ethanol to the astrocyte culture medium for 14 days resulted in an increase in the CYP2E1 content, as determined by confocal microscopy and dot blot. In addition, ethanol induced a dose‐dependent increase in the formation of reactive oxygen species that was partially prevented by incubating the astrocytes with anti‐CYP2E1. Alcohol also induced a dose‐dependent increase in malonaldehyde and hydroxynonenal formation and a depletion of the glutathione (GSH) content. These results suggest that ethanol induces oxidative damage in astrocytes, which could explain some of the toxic effects of ethanol on these cells, such as cytoskeletal alterations. This assumption is supported here by the fact that an increase in GSH content prevents the deleterious effects of alcohol on the cytoskeleton of astrocytes. These results suggest that importance of oxidative stress as a mechanism involved in alcohol‐induced neural and brain damage.
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The role of CYP2E1 in brain ethanol metabolism and its association with alcohol-mediated oxidative neuronal injury and aging-related AD and PD have been suggested.
“The role of CYP2E1 in brain ethanol metabolism and its association with alcohol-mediated oxidative neuronal injury155–160 and aging-related AD and PD161 have also been suggested.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [156]
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- Authors
- Montoliu, C., Sancho‐Tello, M., Azorin, I., Burgal, M., Vallés, S., Renau‐Piqueras, J., & Guerri, C.
- Affiliations
- Instituto de Investigación Sanitaria La Fe (ES)
- Corresponding author
- Guerri, C.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1995-12
- Volume
- 65
- Issue
- 6
- Pages
- 2561-2570
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2017219584
- Cited by
- 218
- References
- 27
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 4 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 5 · 2018: 3 · 2017: 5 · 2016: 6 · 2015: 8 · 2014: 10 · 2013: 7 · 2012: 11
- FWCI
- 5.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- ethanol, CYP2E1, astrocytes, oxidative stress, reactive oxygen species, glutathione depletion, malondialdehyde, 4-hydroxynonenal, alcohol neurotoxicity, cytoskeletal alterations, glial fibrillary acidic protein, nuclear membrane localization
- MeSH terms
- Ethanol, Animals, Astrocytes, Cells, Cultured, Cytochrome P-450 Enzyme System, Glutathione, Lipid Peroxides, Microsomes, Oxidoreductases, N-Demethylating, Reactive Oxygen Species, Oxidative Stress, Cytochrome P-450 CYP2E1, Rats
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