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

par Chrétien, Aline;Dierick, Jean-Francois ;Delaive, Edouard;Larsen, Martin Røssel;Dieu, Marc;Raes, Martine;Deroanne, Christophe;Roepstorff, Peter;Toussaint, Olivier
Référence Free radical biology & medicine, 44, 9, page (1732-1751)
Publication Publié, 2008-05

Article révisé par les pairs

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Résumé :

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. © 2008 Elsevier Inc. All rights reserved.