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 p38 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 HO and onward. This study further clarified the mechanisms of senescence-like morphogenesis in addition to the previously demonstrated role of TGF-β1 signaling pathways.
|Pages (de - à)||1732-1751|
|Nombre de pages||20|
|journal||Free Radical Biology and Medicine|
|Numéro de publication||9|
|Etat de la publication||Publié - 1 mai 2008|
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