Role of TGF-β1-independent changes in protein neosynthesis, p38αMAPK, and cdc42 in hydrogen peroxide-induced senescence-like morphogenesis

The role of TGF-β1 in hydrogen peroxide-induced senescence-like morphogenesis has been described. The aim of this work was to investigate whether TGF-β1-independent changes in protein synthesis are involved in this morphogenesis and to study possible mechanisms occurring earlier than TGF-β1 overexpression. Among the multiple TGF-β1-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 p38MAPK activation, in turn triggering phosphorylation of L-caldesmon and HSP27. Cdc42 was also shown to be mainly responsible for the increase in TGF-β1 mRNA level observed at 24 h after treatment with H2O2 and onward. This study further clarified the mechanisms of senescence-like morphogenesis in addition to the previously demonstrated role of TGF-β1 signaling pathways.