ArticleBiochemical and biophysical research communications2010
Impaired methylation as a novel mechanism for proteasome suppression in liver cells.
Article in Biochemical and biophysical research communications, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Deletion of phosphatidylethanolamine methyltransferase promotes the spontaneous development of hepatic steatosis, inflammation, and fibrosis in young mice.Clinical science (London, England : 1979) · 2026Article
- Hepatocyte-Specific Deletion of Betaine-Homocysteine Methyltransferase Disrupts Methionine Metabolism and Promotes the Spontaneous Development of Hepatic Steatosis.Biomolecules · 2026Article
- Aging Promotes Spontaneous Liver Injury: Insights from Metabolic, Inflammatory, and Fibrotic Pathways in C57BL/6 Mice.Biomolecules · 2025Article
- Betaine regulates the gut-liver axis: a therapeutic approach for chronic liver diseases.Frontiers in nutrition · 2025Review
- Alcohol: basic and translational research; 15th annual Charles Lieber &1st Samuel French satellite symposium.Experimental and molecular pathology · 2022Review
- Acute ethanol-induced liver injury is prevented by betaine administration.Frontiers in physiology · 2022Article
- Beneficial Effects of Betaine: A Comprehensive Review.Biology · 2021Review
- Proteasome Biology: Chemistry and Bioengineering Insights.Polymers · 2020Review
- Rho-kinase ROCK inhibitors reduce oligomeric tau protein.Neurobiology of aging · 2020Article
- Regulation of Proteasome Activity by (Post-)transcriptional Mechanisms.Frontiers in molecular biosciences · 2019Review
- Homocysteine Increases Tau Phosphorylation, Truncation and Oligomerization.International journal of molecular sciences · 2018Article
- Prolonged feeding with guanidinoacetate, a methyl group consumer, exacerbates ethanol-induced liver injury.World journal of gastroenterology · 2016Article
- Proteasome- and ethanol-dependent regulation of HCV-infection pathogenesis.Biomolecules · 2014Review
- Regulation of cardiac proteasomes by ubiquitination, SUMOylation, and beyond.Journal of molecular and cellular cardiology · 2014Review
- Impact of altered methylation in cytokine signaling and proteasome function in alcohol and viral-mediated diseases.Alcoholism, clinical and experimental research · 2013Review
- Ethanol and hepatitis C virus suppress peptide-MHC class I presentation in hepatocytes by altering proteasome function.Alcoholism, clinical and experimental research · 2012Article
- S-adenosylmethionine in liver health, injury, and cancer.Physiological reviews · 2012Review
- Aberrant hepatic methionine metabolism and gene methylation in the pathogenesis and treatment of alcoholic steatohepatitis.International journal of hepatology · 2012Article
- Betaine treatment attenuates chronic ethanol-induced hepatic steatosis and alterations to the mitochondrial respiratory chain proteome.International journal of hepatology · 2012Article
- Purification of CFTR for mass spectrometry analysis: identification of palmitoylation and other post-translational modifications.Protein engineering, design & selection : PEDS · 2012Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The proteasome is a multi-catalytic protein degradation enzyme that is regulated by ethanol-induced oxidative stress; such suppression is attributed to CYP2E1-generated metabolites. However, under certain conditions, it appears that in addition to oxidative stress, other mechanisms are also involved in proteasome regulation. This study investigated whether impaired protein methylation that occurs during exposure of liver cells to ethanol, may contribute to suppression of proteasome activity. We measured the chymotrypsin-like proteasome activity in Huh7CYP cells, hepatocytes, liver cytosols and nuclear extracts or purified 20S proteasome under conditions that maintain or prevent protein methylation. Reduction of proteasome activity of hepatoma cell and hepatocytes by ethanol or tubercidin was prevented by simultaneous treatment with S-adenosylmethionine (SAM). Moreover, the tubercidin-induced decline in proteasome activity occurred in both nuclear and cytosolic fractions. In vitro exposure of cell cytosolic fractions or highly purified 20S proteasome to low SAM:S-adenosylhomocysteine (SAH) ratios in the buffer also suppressed proteasome function, indicating that one or more methyltransferase(s) may be associated with proteasomal subunits. Immunoblotting a purified 20S rabbit red cell proteasome preparation using methyl lysine-specific antibodies revealed a 25kDa proteasome subunit that showed positive reactivity with anti-methyl lysine. This reactivity was modified when 20S proteasome was exposed to differential SAM:SAH ratios. We conclude that impaired methylation of proteasome subunits suppressed proteasome activity in liver cells indicating an additional, yet novel mechanism of proteasome activity regulation by ethanol.
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Registered trials
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