Activation of p38MAPK by TGF-beta in fetal rat hepatocytes requires radical oxygen production, but is dispensable for cell death.
We have previously found that transforming growth factor-beta (TGF-beta) induces 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 may be responsible for this activation. Activation of p38MAPK occurs late, coincident with the maximal production of ROS, it is inhibited by radical scavengers and it is accentuated by the presence of glutathione synthesis inhibitors. However, p38MAPK does not appear to be involved in any of the apoptotic events: loss of Bcl-x(L) levels, cytochrome c release, cleavage of caspase substrates and loss of cell viability.
Herrera
B
B
Departamento de Bioquímica y Biología Molecular (Centro Mixto CSIC/UCM), Facultad de Farmacia, Universidad Complutense de Madrid, Ciudad Universitaria, 28040, Madrid, Spain.
Fernández
M
M
Roncero
C
C
Ventura
J J
JJ
Porras
A
A
Valladares
A
A
Benito
M
M
Fabregat
I
I
D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003574:Cytochrome c Group / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005333:Fetus / Q000166:cytology; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D051020:bcl-X Protein; D048051:p38 Mitogen-Activated Protein Kinases
C494813:Bcl2l1 protein, rat; D003574:Cytochrome c Group; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D051020:bcl-X Protein; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases