Activation of p38MAPK by TGF-beta in fetal rat hepatocytes requires radical oxygen production, but is dispensable for cell death

We hare previously found that transforming growth factor-beta (TGF-beta) in duces an increase in radical oxygen species (ROS) production that mediates its apoptotic effects in fetal hepatocytes, In this paper we show that TGF- beta activates p38 mitogen-activated protein kinase (p38MAPK) and ROS mag b e responsible for this activation. Activation of p38MAPK occurs late, coinc ident with the maximal production of ROS, it is inhibited by radical scaven gers and it is accentuated by the presence of glutathione synthesis inhibit ors. However, p38MAPK does not appear to be involved in any of the apoptoti c events: loss of Bcl-x(L) levels, cytochrome c release, cleavage of caspas e substrates and loss of cell viability, (C) 2001 Federation of European Bi ochemical Societies. Published by Elsevier Science B.V. All rights reserved .