ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2015
Acetaldehyde accelerates HCV-induced impairment of innate immunity by suppressing methylation reactions in liver cells.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Pooled it
- Dynamic Shifts in ER-Plasma Membrane Junctions Signaling Define Pro-Metastatic N-Glycosylation and Predict Prostate Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Ethanol Disrupts the Protective Crosstalk Between Macrophages and HBV-Infected Hepatocytes.Biomolecules · 2025Article
- Like a Rolling Stone? A Review on Spontaneous Clearance of Hepatitis C Virus Infection.Viruses · 2024Review
- Ethanol Exposure to Ethanol-Oxidizing HEPG2 Cells Induces Intracellular Protein Aggregation.Cells · 2023Article
- Unraveling the Complex Interplay between Epigenetics and Immunity in Alcohol-Associated Liver Disease: A ComprehensiveInternational journal of biological sciences · 2023Review
- Cytochrome P450 2E1-dependent hepatic ethanol metabolism induces fatty acid-binding protein 4 and steatosis.Alcoholism, clinical and experimental research · 2022Article
- Beneficial Effects of Betaine: A Comprehensive Review.Biology · 2021Review
- Role of ALDH2 in Hepatic Disorders: Gene Polymorphism and Disease Pathogenesis.Journal of clinical and translational hepatology · 2021Review
- Second hits exacerbate alcohol-related organ damage: an update.Alcohol and alcoholism (Oxford, Oxfordshire) · 2021Review
- Methionine metabolism in chronic liver diseases: an update on molecular mechanism and therapeutic implication.Signal transduction and targeted therapy · 2020Review
- Acetaldehyde suppresses HBV-MHC class I complex presentation on hepatocytes via induction of ER stress and Golgi fragmentation.American journal of physiology. Gastrointestinal and liver physiology · 2020Article
- Role of non-Genetic Risk Factors in Exacerbating Alcohol-related organ damage.Alcohol (Fayetteville, N.Y.) · 2020Review
- Role of alcohol in pathogenesis of hepatitis B virus infection.World journal of gastroenterology · 2020Review
- Aldehyde Dehydrogenase, Liver Disease and Cancer.International journal of biological sciences · 2020Review
- Alcohol Metabolism Potentiates HIV-Induced Hepatotoxicity: Contribution to End-Stage Liver Disease.Biomolecules · 2019Article
- Betaine alleviates high glucose‑induced mesangial cell proliferation by inhibiting cell proliferation and extracellular matrix deposition via the AKT/ERK1/2/p38 MAPK pathway.Molecular medicine reports · 2019Article
- Acetaldehyde suppresses the display of HBV-MHC class I complexes on HBV-expressing hepatocytes.American journal of physiology. Gastrointestinal and liver physiology · 2019Article
- The Role of Alcohol-Induced Golgi Fragmentation for Androgen Receptor Signaling in Prostate Cancer.Molecular cancer research : MCR · 2019Article
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Alcohol exposure worsens the course and outcomes of hepatitis C virus (HCV) infection. Activation of protective antiviral genes is induced by IFN-α signaling, which is altered in liver cells by either HCV or ethanol exposure. However, the mechanisms of the combined effects of HCV and ethanol metabolism in IFN-α signaling modulation are not well elucidated. Here, we explored a possibility that ethanol metabolism potentiates HCV-mediated dysregulation of IFN-α signaling in liver cells via impairment of methylation reactions. HCV-infected Huh7.5 CYP2E1(+) cells and human hepatocytes were exposed to acetaldehyde (Ach)-generating system (AGS) and stimulated with IFN-α to activate IFN-sensitive genes (ISG) via the Jak-STAT-1 pathway. We observed significant suppression of signaling events by Ach. Ach exposure decreased STAT-1 methylation via activation of protein phosphatase 2A and increased the protein inhibitor of activated STAT-1 (PIAS-1)-STAT-1 complex formation in both HCV(+) and HCV(-) cells, preventing ISG activation. Treatment with a promethylating agent, betaine, attenuated all examined Ach-induced defects. Ethanol metabolism-induced changes in ISGs are methylation related and confirmed by in vivo studies on HCV(+) transgenic mice. HCV- and Ach-induced impairment of IFN signaling temporarily increased HCV RNA levels followed by apoptosis of heavily infected cells. We concluded that Ach potentiates the suppressive effects of HCV on activation of ISGs attributable to methylation-dependent dysregulation of IFN-α signaling. A temporary increase in HCV RNA sensitizes the liver cells to Ach-induced apoptosis. Betaine reverses the inhibitory effects of Ach on IFN signaling and thus can be used for treatment of HCV(+) alcohol-abusing patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.