| Microtubules are more stable and more highly acetylated in ethanol-treated hepatic cells. | |
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MedLine Citation:
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PMID: 16169115 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND/AIMS: Chronic alcohol consumption can lead to serious liver disease. Although the disease progression is clinically well-described, the molecular basis for alcohol-induced hepatotoxicity is not understood. METHODS: We examined hepatocyte-specific, alcohol-induced alterations in microtubule dynamics in WIF-B cells. These cells provide an excellent model for studying alcohol-induced hepatotoxicity; they remain differentiated in culture and metabolize alcohol. RESULTS: Consistent with reports in other hepatic systems, microtubule polymerization in ethanol-treated WIF-B cells was impaired. However, when viewed by epifluorescence, the microtubules in ethanol-treated cells resembled stable polymers. Antibodies to acetylated alpha-tubulin confirmed their identity morphologically and revealed biochemically that ethanol-treated cells had approximately three-fold more acetylated alpha-tubulin than control cells. Livers from ethanol-fed rats also contained increased levels of acetylated alpha-tubulin. Consistent with increased acetylated alpha-tubulin levels, microtubules in ethanol-treated WIF-B cells were more stable. Because stability increased with increased time of ethanol exposure or concentration, was prevented by 4-methylpyrazole and was potentiated by cyanamide, we conclude that increased acetylation requires alcohol metabolism and is likely to be mediated by acetaldehyde. CONCLUSIONS: Ethanol metabolism impairs tubulin polymerization, but once microtubules are formed they are hyperstabilized. These ethanol-induced alterations in microtubule integrity likely have profound effects on hepatocyte function. |
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Authors:
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George T Kannarkat; Dean J Tuma; Pamela L Tuma |
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Publication Detail:
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Type: Journal Article Date: 2005-07-27 |
Journal Detail:
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Title: Journal of hepatology Volume: 44 ISSN: 0168-8278 ISO Abbreviation: J. Hepatol. Publication Date: 2006 May |
Date Detail:
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Created Date: 2006-04-17 Completed Date: 2006-09-27 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8503886 Medline TA: J Hepatol Country: England |
Other Details:
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Languages: eng Pagination: 963-70 Citation Subset: IM |
Affiliation:
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Department of Biology, The Catholic University of America, 620 Michigan Avenue, NE, Washington, DC 20064, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetaldehyde
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metabolism Acetylation / drug effects Animals Carcinoma, Hepatocellular Cell Line, Tumor Central Nervous System Depressants / pharmacokinetics, toxicity* Ethanol / pharmacokinetics, toxicity* Hepatocytes / cytology, drug effects*, metabolism Liver Diseases, Alcoholic / metabolism, pathology* Liver Neoplasms Microtubules / drug effects*, metabolism Polymers / metabolism Rats |
| Chemical | |
Reg. No./Substance:
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0/Central Nervous System Depressants; 0/Polymers; 64-17-5/Ethanol; 75-07-0/Acetaldehyde |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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