[en] 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Chretien, Aline; University of Namur > Research Unit on Cellular Biology
Dierick, Jean-Francois; University of Brussels, Gosselies > Institute of Molecular Biology and Medicine
Delaive, Edouard; University of Southern Denmark, Odense M > Dpt of Biochemistry and Molecular Biology > Protein Research Group
Larsen, Martin Rossel; University of Southern Denmark, Odense M > Dpt of Biochemistry and Molecular Biology > Protein Research Group
Dieu, Marc; University of Namur > Research Unit on Cellular Biology
Raes, Martine; University of Namur > Research Unit on Cellular Biology
Deroanne, Christophe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Laboratoire des tissus conjonctifs
Roepstorff, Peter; University of Southern Denmark, Odense M > Dpt of Biochemistry and Molecular Biology > Protein Research Group
Toussaint, Olivier; University of Namur > Research Unit on Cellular Biology
Language :
English
Title :
Role of TGF-beta1-independent changes in protein neosynthesis, p38alphaMAPK, and cdc42 in hydrogen peroxide-induced senescence-like morphogenesis.
Publication date :
2008
Journal title :
Free Radical Biology and Medicine
ISSN :
0891-5849
eISSN :
1873-4596
Publisher :
Elsevier Science, Tarrytown, United States - New York
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