ArticlePloS one2012
Ethanol-mediated regulation of cytochrome P450 2A6 expression in monocytes: role of oxidative stress-mediated PKC/MEK/Nrf2 pathway.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 55 citations in OpenAlex.
- Exploring the therapeutic synergy of drug-lifestyle interventions in fluorosis: a randomized trial on cardiovascular metabolic outcomes from the China fluorosis cohort (CFC).Frontiers in pharmacology · 2026Article
- The Multifaceted Role of Cytochrome P450 Isoenzymes in Alcoholic and Metabolic (Dysfunction) Fatty Liver Diseases.Current drug metabolism · 2026Review
- Targeting epigenetic and post-translational modifications of NRF2: key regulatory factors in disease treatment.Cell death discovery · 2025Review
- Acute and long-term effects of cannabinoids on hypertension and kidney injury.Scientific reports · 2022Article
- Nicotine self-administration with menthol and audiovisual cue facilitates differential packaging of CYP2A6 and cytokines/chemokines in rat plasma extracellular vesicles.Scientific reports · 2021Article
- Effects of alcohol-induced increase in CYP2E1 content in human liver microsomes on the activity and cooperativity of CYP3A4.Archives of biochemistry and biophysics · 2021Article
- CYP2E1 changes the biological function of gastric cancer cells via the PI3K/Akt/mTOR signaling pathway.Molecular medicine reports · 2020Article
- Differences in the rate of nicotine metabolism among smokers with and without HIV.AIDS (London, England) · 2019Article
- Cytochrome P450s and Alcoholic Liver Disease.Current pharmaceutical design · 2018Review
- Trichostatin A Shows Transient Protection from Chronic Alcohol-Induced Reactive Oxygen Species (ROS) Production in Human Monocyte-Derived Dendritic Cells.Journal of alcoholism and drug dependence · 2018Article
- Kinetic characterizations of diallyl sulfide analogs for their novel role as CYP2E1 enzyme inhibitors.Pharmacology research & perspectives · 2017Article
- Specific packaging and circulation of cytochromes P450, especially 2E1 isozyme, in human plasma exosomes and their implications in cellular communications.Biochemical and biophysical research communications · 2017Article
- High Level of Tobacco Carcinogen-Derived DNA Damage in Oral Cells Is an Independent Predictor of Oral/Head and Neck Cancer Risk in Smokers.Cancer prevention research (Philadelphia, Pa.) · 2017Article
- Increased ethanol-inducible cytochrome P450-2E1 and cytochrome P450 isoforms in exosomes of alcohol-exposed rodents and patients with alcoholism through oxidative and endoplasmic reticulum stress.Hepatology communications · 2017Article
- Protocatechualdehyde Protects Against Cerebral Ischemia-Reperfusion-Induced Oxidative Injury Via Protein Kinase Cε/Nrf2/HO-1 Pathway.Molecular neurobiology · 2017Article
- Alcoholic Liver Disease: from CYP2E1 to CYP2A5.Current molecular pharmacology · 2017Review
- Article
- Alcohol Upregulation of CYP2A5: Role of Reactive Oxygen Species.Reactive oxygen species (Apex, N.C.) · 2016Article
- Effects of Cigarette Smoke Condensate on Oxidative Stress, Apoptotic Cell Death, and HIV Replication in Human Monocytic Cells.PloS one · 2016Article
- The role of CYP2A5 in liver injury and fibrosis: chemical-specific difference.Naunyn-Schmiedeberg's archives of pharmacology · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cytochrome P450 2A6 (CYP2A6) is known to metabolize nicotine, the major constituent of tobacco, leading to the production of toxic metabolites and induction of oxidative stress that result in liver damage and lung cancer. Recently, we have shown that CYP2A6 is induced by ethanol and metabolizes nicotine into cotinine and other metabolites leading to generation of reactive oxygen species (ROS) in U937 monocytes. However, the mechanism by which CYP2A6 is induced by ethanol is unknown. In this study, we have examined the role of the PKC/Nrf2 pathway (protein kinase C-mediated phosphorylation and translocation of nuclear erythroid 2-related factor 2 to the nucleus) in ethanol-mediated CYP2A6 induction. Our results showed that 100 mM ethanol significantly induced CYP2A6 mRNA and protein (~150%) and increased ROS formation, and induction of gene expression and ROS were both completely blocked by treatment with either a CYP2E1 inhibitor (diallyl sulfide) or an antioxidant (vitamin C). The results suggest the role of oxidative stress in the regulation of CYP2A6 expression. Subsequently, we investigated the role of Nrf2 pathway in oxidative stress-mediated regulation of CYP2A6 expression in U937 monocytes. Our results showed that butylated hydroxyanisole, a stabilizer of nuclear Nrf2, increased CYP2A6 levels >200%. Staurosporine, an inhibitor of PKC, completely abolished ethanol-induced CYP2A6 expression. Furthermore, our results showed that a specific inhibitor of mitogen-activated protein kinase kinase (MEK) (U0126) completely abolished ethanol-mediated CYP2A6 induction and Nrf2 translocation. Overall, these results suggest that CYP2E1-mediated oxidative stress produced as a result of ethanol metabolism translocates Nrf2 into the nucleus through PKC/MEK pathway, resulting in the induction of CYP2A6 in monocytes. An increased level of CYP2A6 in monocytes is expected to further increase oxidative stress in smokers through CYP2A6-mediated nicotine metabolism. Thus, this study has clinical relevance because of the high incidence of alcohol use among smokers, especially in HIV-infected individuals.
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