Ethanol sensitizes primary mouse hepatocytes for the apoptotic effects of transforming growth factor (TGF)-β
K Breitkopf-Heinlein, H Gaitantzi, C Meyer, Q Li, J Dzieran, S Schneider, A Müller, G Millonig, S Mueller, H Bantel, K Wahl, S Dooley · Zeitschrift für Gastroenterologie · 2011 · Heft 08
Bibliografische Angaben
Zusammenfassung
We previously showed that TGF-β signalling is increased in ethanol fed mice and that a combination of ethanol plus TGF-β causes much more apoptosis of primary mouse hepatocytes than each stimulus alone. In the present study we further analyzed this apoptosis induction and show that ethanol strongly enhances TGF-β Smad-signalling in isolated hepatocytes. Apoptosis induction was accompanied by reduced basal activity of Akt along with increased TGF-β receptor type II (TβRII) expression. Blunting PI3K/Akt with the small molecule inhibitor LY294002 in hepatocytes blocked apoptosis and, similar to ethanol, led to incr…