Hepatic microtubule acetylation and stability induced by chronic alcohol exposure impair nuclear translocation of STAT3 and STAT5B, but not Smad2/3.

摘要: Although alcoholic liver disease is clinically well described, the molecular basis for alcohol-induced hepatotoxicity not understood. Previously, we found that alcohol exposure led to increased microtubule acetylation and stability in polarized, hepatic WIF-B cells livers from ethanol-fed rats. Because microtubules are known regulate transcription factor nuclear translocation dynamic required of at least a subset these factors, examined whether impair translocation. We delivery factors representing two mechanisms by which To represent undergo directed delivery, growth hormone-induced STAT5B IL-6-induced STAT3 sequestered cytoplasm attachment until ligand activation, transforming factor-β-induced Smad2/3 ethanol selectively impaired STATs, but Smad2/3. was decreased similar extent addition taxol (a microtubule-stabilizing drug) or trichostatin A deacetylase inhibitor), agents promote absence alcohol. Thus impairment STAT can be explained stability. Only treatment indicating important its activation Jak2. Furthermore, exit changed treated cells, this process also independent Together, results raise exciting possibility agonists may effective therapeutics disease.