Role of TGF-beta1-independent changes in protein neosynthesis, p38alphaMAPK, and cdc42 in hydrogen peroxide-induced senescence-like morphogenesis.
The role of TGF-beta1 in hydrogen peroxide-induced senescence-like morphogenesis has been described. The aim of this work was to investigate whether TGF-beta1-independent changes in protein synthesis are involved in this morphogenesis and to study possible mechanisms occurring earlier than TGF-beta1 overexpression. Among the multiple TGF-beta1-independent changes in protein neosynthesis, followed or not by posttranslational modifications, identified by proteomic analysis herein, those of ezrin, L-caldesmon, and HSP27 were particularly studied. Rho-GTPase cdc42 was shown to be responsible for p38(MAPK) activation, in turn triggering phosphorylation of L-caldesmon and HSP27. Cdc42 was also shown to be mainly responsible for the increase in TGF-beta1 mRNA level observed at 24 h after treatment with H(2)O(2) and onward. This study further clarified the mechanisms of senescence-like morphogenesis in addition to the previously demonstrated role of TGF-beta1 signaling pathways.
Chrétien
Aline
A
Research Unit on Cellular Biology, University of Namur, B-5000 Namur, Belgium.
Dierick
Jean-François
JF
Delaive
Edouard
E
Larsen
Martin Røssel
MR
Dieu
Marc
M
Raes
Martine
M
Deroanne
Christophe F
CF
Roepstorff
Peter
P
Toussaint
Olivier
O
D002148:Calmodulin-Binding Proteins / Q000494:pharmacology; D002470:Cell Survival; D016922:Cellular Senescence; D015180:Electrophoresis, Gel, Two-Dimensional; D005347:Fibroblasts / Q000378:metabolism*; D005609:Free Radicals; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000494:pharmacology*; D008954:Models, Biological; D018384:Oxidative Stress; D010641:Phenotype; D010766:Phosphorylation; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D002148:Calmodulin-Binding Proteins; D005609:Free Radicals; D053773:Transforming Growth Factor beta1; D006861:Hydrogen Peroxide; D048051:p38 Mitogen-Activated Protein Kinases; D020764:cdc42 GTP-Binding Protein