ArticleCell communication and signaling : CCS2020
Higher sensitivity of female cells to ethanol: methylation of DNA lowers Cyp2e1, generating more ROS.
Article in Cell communication and signaling : CCS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 27 citations in OpenAlex.
- Epigenetic deciphering of ovarian aging: multilayer interactive mechanisms and targeted reversal strategies.Epigenetics & chromatin · 2026Review
- Not just neurons: glial mechanisms driving sex-specific vulnerability to withdrawal and relapse in substance use disorder.Frontiers in neuroendocrinology · 2026Review
- DNA methylation regulation of CYP450-lipid metabolism by high-altitude hypoxia: linking neuroinflammation to cognitive impairment.Journal of neuroinflammation · 2026Article
- Mechanism of crosstalk between DNA methylation and histone acetylation and related advances in diagnosis and treatment of premature ovarian failure.Epigenetics · 2025Review
- Reactive Oxygen Species as Key Molecules in the Pathogenesis of Alcoholic Fatty Liver Disease and Nonalcoholic Fatty Liver Disease: Future Perspectives.Current issues in molecular biology · 2025Review
- Sex Difference of Alcoholic Hypertension: Mechanism and Targeted Therapy.Current hypertension reports · 2025Review
- Protective role of 17β-estradiol in alcohol-associated liver fibrosis is mediated by suppression of integrin signaling.Hepatology communications · 2024Article
- Hepatocyte-specific mitogen-activated protein kinase phosphatase 1 in sexual dimorphism and susceptibility to alcohol induced liver injury.Frontiers in immunology · 2024Article
- DNA Methylation in Alcohol Use Disorder.International journal of molecular sciences · 2023Review
- A Pathogenic Role of Non-Parenchymal Liver Cells in Alcohol-Associated Liver Disease of Infectious and Non-Infectious Origin.Biology · 2023Review
- Sex difference in the association between blood alcohol concentration and serum ferritin.Frontiers in psychiatry · 2023Article
- Male-Specific Activation of Lysine Demethylases 5B and 5C Mediates Alcohol-Induced Liver Injury and Hepatocyte Dedifferentiation.Hepatology communications · 2022Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCells taken from mouse embryos before sex differentiation respond to insults according to their chromosomal sex, a difference traceable to differential methylation. We evaluated the mechanism for this difference in the controlled situation of their response to ethanol.
methodsWe evaluated the expression of mRNA for alcohol dehydrogenase (ADH), aldehyde dehyrogenases (ALDH), and a cytochrome P450 isoenzyme (Cyp2e1) in male and female mice, comparing the expressions to toxicity under several experimental conditions evaluating redox and other states.
resultsFemales are more sensitive to ethanol. Disulfiram, which inhibits alcohol dehydrogenase (ADH), increases cell death in males, eliminating the sex dimorphism. The expressions ADH Class 1 to 4 and ALDH Class 1 and 2 do not differ by sex. However, females express approximately 8X more message for Cyp2e1, an enzyme in the non-canonical pathway. Female cells produce approximately 15% more ROS (reactive oxygen species) than male cells, but male cells contain approximately double the concentration of GSH, a ROS scavenger. Scavenging ROS with N-acetyl cysteine reduces cell death and eliminates sex dimorphism. Finally, since many of the differences in gene expression derive from methylation of DNA, we exposed cells to the methyltransferase inhibitor 5-aza- 2-deoxycytidine; blocking methylation eliminates both the difference in expression of Cyp2e1 and cell death.
conclusionWe conclude that the sex-differential cell death caused by ethanol derives from sex dimorphic methylation of Cyp2e1 gene, resulting in generation of more ROS.
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