ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2010
Inhibitory effect of ethanol on AMPK phosphorylation is mediated in part through elevated ceramide levels.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 79 citations in OpenAlex.
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- Inhibition of sphingomyelinase attenuates diet - Induced increases in aortic stiffness.Journal of molecular and cellular cardiology · 2022Article
- Betaine in ameliorating alcohol-induced hepatic steatosis.European journal of nutrition · 2022Review
- Implications of pre-transplant sarcopenia and frailty in patients with non-alcoholic steatohepatitis and alcoholic liver disease.Translational gastroenterology and hepatology · 2022Review
- Pathogenesis of Alcohol-Associated Fatty Liver: Lessons From Transgenic Mice.Frontiers in physiology · 2022Review
- A review of the role of ethanol-induced adipose tissue dysfunction in alcohol-associated liver disease.Alcoholism, clinical and experimental research · 2021Review
- Beneficial Effects of Betaine: A Comprehensive Review.Biology · 2021Review
- Activated Protein Phosphatase 2A Disrupts Nutrient Sensing Balance Between Mechanistic Target of Rapamycin Complex 1 and Adenosine Monophosphate-Activated Protein Kinase, Causing Sarcopenia in Alcohol-Associated Liver Disease.Hepatology (Baltimore, Md.) · 2021Article
- 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
- Liver-specific ceramide reduction alleviates steatosis and insulin resistance in alcohol-fed mice.Journal of lipid research · 2020Article
- Article
- The Metformin Mechanism on Gluconeogenesis and AMPK Activation: The Metabolite Perspective.International journal of molecular sciences · 2020Review
- Alcohol effects on hepatic lipid metabolism.Journal of lipid research · 2020Review
- Ethanol sensitizes skeletal muscle to ammonia-induced molecular perturbations.The Journal of biological chemistry · 2019Article
- Ethanol and C2 ceramide activate fatty acid oxidation in human hepatoma cells.Scientific reports · 2018Article
- Activation of neutral sphingomyelinase 2 by starvation induces cell-protective autophagy via an increase in Golgi-localized ceramide.Cell death & disease · 2018Article
- The role of sphingolipids in psychoactive drug use and addiction.Journal of neural transmission (Vienna, Austria : 1996) · 2018Review
- A novel role for ceramide synthase 6 in mouse and human alcoholic steatosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Ethanol treatment of cultured hepatoma cells and of mice inhibited the activity of AMP-activated protein kinase (AMPK). This study shows that the inhibitory effect of ethanol on AMPK phosphorylation is exerted through the inhibition of the phosphorylation of upstream kinases and the activation of protein phosphatase 2A (PP2A).Inhibition of AMPK phosphorylation by palmitate was attributed to ceramide-dependent PP2A activation. We hypothesized that the inhibitory effect of ethanol on AMPK phosphorylation was mediated partly through the generation of ceramide. The effect of ethanol and inhibitors of ceramide synthesis on AMPK phosphorylation, ceramide levels, and PP2A activity were assessed in rat hepatoma cells (H4IIEC3). The effect of ethanol on hepatic ceramide levels was also studied in C57BL/6J mice fed the Lieber-DeCarli diet. In H4IIEC3 cells, ceramide reduced AMPK phosphorylation when they were treated for between 4 and 12 h. The basal level of AMPK phosphorylation in hepatoma cells was increased with the treatment of ceramide synthase inhibitor, fumonisin B1. Ethanol treatment significantly increased cellular ceramide content and PP2A activity by approximately 18-23%, when the cells were treated with ethanol for between 4 and 12 h. These changes in intracellular ceramide concentrations and PP2A activity correlated with the time course over which ethanol inhibited AMPK phosphorylation. The activation of PP2A and inhibition of AMPK phosphorylation caused by ethanol was attenuated by fumonisin B1 and imipramine, an acid sphingomyelinase (SMase) inhibitor. There was a significant increase in the levels of ceramide and acid SMase mRNA in the livers of ethanol-fed mice compared with controls. We concluded that the effect of ethanol on AMPK appears to be mediated in part through increased cellular levels of ceramide and activation of PP2A.
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