ArticleThe Journal of biological chemistry2014
Identification of 5' AMP-activated kinase as a target of reactive aldehydes during chronic ingestion of high concentrations of ethanol.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- The Role of Oxidative Stress in Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Preclinical Studies.Nutrients · 2024Pooled it
- Dysregulated hepatic alcohol metabolism: a key factor involved in the pathogenesis of alcohol-associated liver disease.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Liver diseases: epidemiology, causes, trends and predictions.Signal transduction and targeted therapy · 2025Review
- Alcohol and its metabolites dysregulate cellular bioenergetics and induce oxidative and endoplasmic reticulum stress in primary human bronchial epithelial cells.Alcohol, clinical & experimental research · 2024Article
- New insights in the pathogenesis of alcohol-related liver disease: The metabolic, immunologic, and neurologic pathwaysLiver research (Beijing, China) · 2023Review
- Identifying chemicals based on receptor binding/bioactivation/mechanistic explanation associated with potential to elicit hepatotoxicity and to support structure activity relationship-based read-across.Current research in toxicology · 2023Article
- The autophagic protein p62 is a target of reactive aldehydes in human and murine cholestatic liver disease.PloS one · 2022Article
- Oxidative Stress-A Key Player in the Course of Alcohol-Related Liver Disease.Journal of clinical medicine · 2021Review
- Differential cytotoxicity, ER/oxidative stress, dysregulated AMPKα signaling, and mitochondrial stress by ethanol and its metabolites in human pancreatic acinar cells.Alcoholism, clinical and experimental research · 2021Article
- Protein Lipoxidation: Basic Concepts and Emerging Roles.Antioxidants (Basel, Switzerland) · 2021Review
- Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury.Experimental & molecular medicine · 2021Review
- Activation of AMP-activated protein kinase attenuates ethanol-induced ER/oxidative stress and lipid phenotype in human pancreatic acinar cells.Biochemical pharmacology · 2020Article
- Role of non-Genetic Risk Factors in Exacerbating Alcohol-related organ damage.Alcohol (Fayetteville, N.Y.) · 2020Review
- Alcohol Metabolizing Enzymes, Microsomal Ethanol Oxidizing System, Cytochrome P450 2E1, Catalase, and Aldehyde Dehydrogenase in Alcohol-Associated Liver Disease.Biomedicines · 2020Review
- Lipid peroxidation derived reactive aldehydes in alcoholic liver disease.Current opinion in toxicology · 2019Article
- AMPK-ERK/CARM1 Signaling Pathways Affect Autophagy of Hepatic Cells in Samples of Liver Cancer Patients.Frontiers in oncology · 2019Article
- Transgenic overexpression of CTRP3 prevents alcohol-induced hepatic triglyceride accumulation.American journal of physiology. Endocrinology and metabolism · 2018Article
- Knockout of the Gsta4 Gene in Male Mice Leads to an Altered Pattern of Hepatic Protein Carbonylation and Enhanced Inflammation Following Chronic Consumption of an Ethanol Diet.Alcoholism, clinical and experimental research · 2018Article
- Dysregulation of antioxidant responses in patients diagnosed with concomitant Primary Sclerosing Cholangitis/Inflammatory Bowel Disease.Experimental and molecular pathology · 2018Article
- Aldehyde-Induced DNA and Protein Adducts as Biomarker Tools for Alcohol Use Disorder.Trends in molecular medicine · 2018Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The production of reactive aldehydes including 4-hydroxy-2-nonenal (4-HNE) is a key component of the pathogenesis in a spectrum of chronic inflammatory hepatic diseases including alcoholic liver disease (ALD). One consequence of ALD is increased oxidative stress and altered β-oxidation in hepatocytes. A major regulator of β-oxidation is 5' AMP protein kinase (AMPK). In an in vitro cellular model, we identified AMPK as a direct target of 4-HNE adduction resulting in inhibition of both H2O2 and 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR)-induced downstream signaling. By employing biotin hydrazide capture, it was confirmed that 4-HNE treatment of cells resulted in carbonylation of AMPKα/β, which was not observed in untreated cells. Using a murine model of alcoholic liver disease, treatment with high concentrations of ethanol resulted in an increase in phosphorylated as well as carbonylated AMPKα. Despite increased AMPK phosphorylation, there was no significant change in phosphorylation of acetyl CoA carboxylase. Mass spectrometry identified Michael addition adducts of 4-HNE on Cys(130), Cys(174), Cys(227), and Cys(304) on recombinant AMPKα and Cys(225) on recombinant AMPKβ. Molecular modeling analysis of identified 4-HNE adducts on AMPKα suggest that inhibition of AMPK occurs by steric hindrance of the active site pocket and by inhibition of hydrogen peroxide induced oxidation. The observed inhibition of AMPK by 4-HNE provides a novel mechanism for altered β-oxidation in ALD, and these data demonstrate for the first time that AMPK is subject to regulation by reactive aldehydes in vivo.
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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.