Microtubules are more stable and more highly acetylated in ethanol-treated hepatic cells

George T. Kannarkat, Dean J. Tuma, Pamela L. Tuma

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

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 α-tubulin confirmed their identity morphologically and revealed biochemically that ethanol-treated cells had approximately three-fold more acetylated α-tubulin than control cells. Livers from ethanol-fed rats also contained increased levels of acetylated α-tubulin. Consistent with increased acetylated α-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.

Original languageEnglish (US)
Pages (from-to)963-970
Number of pages8
JournalJournal of Hepatology
Volume44
Issue number5
DOIs
Publication statusPublished - May 1 2006

    Fingerprint

Keywords

  • Acetaldehyde
  • Acetylation
  • Alcohol
  • Hepatocytes
  • Microtubules
  • WIF-B cells

ASJC Scopus subject areas

  • Hepatology

Cite this