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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2002-7-10
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pubmed:abstractText |
Chronic ethanol consumption is associated with increased protein oxidation and decreased proteolysis in the liver. We tested the hypothesis that even single-dose treatment with ethanol or bromotrichloromethane causes increased protein oxidation and a distinct proteolytic response in cultured hepatocytes. HepG2 cells were treated for 30 min with ethanol, H(2)O(2) and bromotrichloromethane at various nontoxic concentrations. Protein degradation was measured in living cells using [35S]-methionine labeling. Protein oxidation, and 20S proteasome activity were measured in cell lysates. Oxidized proteins increased immediately after ethanol, H(2)O(2), and bromotrichloromethane exposure, but a further significant increase 24-h after exposure was observed only following ethanol and bromotrichloromethane treatment. All three reagents caused a significant increase of the overall intracellular proteolysis at rather low concentrations, which could be suppressed by the proteasome inhibitor lactacystin. A decline of proteolysis observed at higher-subtoxic-concentrations was not related to decreased proteasome activity. Preincubation with ketoconazole or 4-methylpyrazole completely prevented the ethanol- and bromotrichloromethane-induced but not the H(2)O(2)-induced protein oxidation and proteolysis, suggesting strongly an enzyme-mediated generation of reactive oxygen species. In conclusion single-dose exposure with ethanol or haloalkanes causes increased protein oxidation followed by an increased proteasome-dependent protein degradation in human liver cells.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bromotrichloromethane,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Ethanol,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0891-5849
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
33
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
283-91
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12106824-Bromotrichloromethane,
pubmed-meshheading:12106824-Cell Survival,
pubmed-meshheading:12106824-Cells, Cultured,
pubmed-meshheading:12106824-Cysteine Endopeptidases,
pubmed-meshheading:12106824-Cytochrome P-450 Enzyme System,
pubmed-meshheading:12106824-DNA Primers,
pubmed-meshheading:12106824-Dose-Response Relationship, Drug,
pubmed-meshheading:12106824-Enzyme Inhibitors,
pubmed-meshheading:12106824-Ethanol,
pubmed-meshheading:12106824-Hepatocytes,
pubmed-meshheading:12106824-Humans,
pubmed-meshheading:12106824-Hydrogen Peroxide,
pubmed-meshheading:12106824-Multienzyme Complexes,
pubmed-meshheading:12106824-Oxidation-Reduction,
pubmed-meshheading:12106824-Oxidative Stress,
pubmed-meshheading:12106824-Polymerase Chain Reaction,
pubmed-meshheading:12106824-Proteasome Endopeptidase Complex,
pubmed-meshheading:12106824-Proteins,
pubmed-meshheading:12106824-RNA,
pubmed-meshheading:12106824-Reactive Oxygen Species
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pubmed:year |
2002
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pubmed:articleTitle |
Increased proteolysis after single-dose exposure with hepatotoxins in HepG2 cells.
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pubmed:affiliation |
Department of Gastroenterology and Hepatology, University Hospital Charité, Humboldt-University Berlin, Germany.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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