ArticleThe Journal of biological chemistry2012
Ethanol suppresses ureagenesis in rat hepatocytes: role of acetaldehyde.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 52 citations in OpenAlex.
- Probiotics as Potential Therapeutic Agents: Safeguarding Skeletal Muscle against Alcohol-Induced Damage through the Gut-Liver-Muscle Axis.Biomedicines · 2024Review
- Potential Benefits of Epidermal Growth Factor for Inhibiting Muscle Degrative Markers in Rats with Alcoholic Liver Damage.International journal of molecular sciences · 2023Article
- Metabolic signature of HepaRG cells exposed to ethanol and tumor necrosis factor alpha to study alcoholic steatohepatitis by LC-MS-based untargeted metabolomics.Archives of toxicology · 2023Article
- Mitochondrial depolarization after acute ethanol treatment drives mitophagy in living mice.Autophagy · 2022Article
- Mechanism Analysis of Metabolic Fatty Liver on Largemouth Bass (Metabolites · 2022Article
- Impact of Sarcopenia and Myosteatosis in Non-Cirrhotic Stages of Liver Diseases: Similarities and Differences across Aetiologies and Possible Therapeutic Strategies.Biomedicines · 2022Review
- Metabolic implications of non-electrogenic ATP/ADP exchange in cancer cells: A mechanistic basis for the Warburg effect.Biochimica et biophysica acta. Bioenergetics · 2021Review
- Mitochondrial dysfunction and liver disease: role, relevance, and potential for therapeutic modulation.Therapeutic advances in gastroenterology · 2021Review
- VDAC1 at the Intersection of Cell Metabolism, Apoptosis, and Diseases.Biomolecules · 2020Review
- Ethanol exposure increases mutation rate through error-prone polymerases.Nature communications · 2020Article
- The gut microbiome and its potential role in paradoxical anaerobism in pupfishes of the Mojave Desert.Animal microbiome · 2020Article
- Alcohol effects on hepatic lipid metabolism.Journal of lipid research · 2020Review
- A Mitochondrial VDAC1-Based Peptide Greatly Suppresses Steatosis and NASH-Associated Pathologies in a Mouse Model.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Ethanol sensitizes skeletal muscle to ammonia-induced molecular perturbations.The Journal of biological chemistry · 2019Article
- Effect of ethanol on lipid metabolism.Journal of hepatology · 2019Review
- A Unifying Hypothesis Linking Hepatic Adaptations for Ethanol Metabolism to the Proinflammatory and Profibrotic Events of Alcoholic Liver Disease.Alcoholism, clinical and experimental research · 2018Review
- Mitophagy in hepatocytes: Types, initiators and role in adaptive ethanol metabolism☆.Liver research (Beijing, China) · 2018Article
- Nutrition and Muscle in Cirrhosis.Journal of clinical and experimental hepatology · 2017Review
- Sarcopenia in Alcoholic Liver Disease: Clinical and Molecular Advances.Alcoholism, clinical and experimental research · 2017Review
- Glutamate contributes to alcohol hepatotoxicity by enhancing oxidative stress in mitochondria.Journal of bioenergetics and biomembranes · 2017Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
We proposed previously that closure of voltage-dependent anion channels (VDAC) in the mitochondrial outer membrane after ethanol exposure leads to suppression of mitochondrial metabolite exchange. Because ureagenesis requires extensive mitochondrial metabolite exchange, we characterized the effect of ethanol and its metabolite, acetaldehyde (AcAld), on total and ureagenic respiration in cultured rat hepatocytes. Ureagenic substrates increased cellular respiration from 15.8 ± 0.9 nmol O(2)/min/10(6) cells (base line) to 29.4 ± 1.7 nmol O(2)/min/10(6) cells in about 30 min. Ethanol (0-200 mM) suppressed extra respiration after ureagenic substrates (ureagenic respiration) by up to 51% but not base line respiration. Urea formation also declined proportionately. Inhibition of alcohol dehydrogenase, cytochrome P450 2E1, and catalase with 4-methylpyrazole, trans-1,2-dichloroethylene, and 3-amino-1,2,3-triazole restored ethanol-suppressed ureagenic respiration by 46, 37, and 66%, respectively. By contrast, inhibition of aldehyde dehydrogenase with phenethyl isothiocyanate increased the inhibitory effect of ethanol on ureagenic respiration by an additional 60%. AcAld, an intermediate product of ethanol oxidation, suppressed ureagenic respiration with an apparent IC(50) of 125 μM. AcAld also inhibited entry of 3-kDa rhodamine-conjugated dextran in the mitochondrial intermembrane space of digitonin-permeabilized hepatocytes, indicative of VDAC closure. In conclusion, AcAld, derived from ethanol metabolism, suppresses ureagenesis in hepatocytes mediated by closure of VDAC.
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