Role of TGF-β1-independent changes in protein neosynthesis, p380αMAPK and cdc42 in hydrogen peroxide-induced senescence-like morphogenesis

被引:18
作者
Chretien, Aline [1 ]
Dierick, Jean-Francois [2 ]
Delaive, Edouard [1 ]
Larsen, Martin Rossel [3 ]
Dieu, Marc [1 ]
Raes, Martine [1 ]
Deroanne, Christophe F. [4 ]
Roepstorff, Peter [3 ]
Toussaint, Olivier [1 ]
机构
[1] Univ Namur, Res Unit Cellular Biol, B-5000 Namur, Belgium
[2] Univ Brussels, Inst Mol Biol & Med, Gosselies, Belgium
[3] Univ So Denmark, Dept Biochem & Mol Biol, Prot Res Grp, Odense M, Denmark
[4] Univ Liege, CBIG GIGA Res Ctr, Lab Connect Tissues Biol, Sart Tilman Par Liege, Belgium
关键词
H2O2; neosynthesis; proteomics; siRNA; senescence; cdc42; p38(MAPK); free radicals;
D O I
10.1016/j.freeradbiomed.2008.01.026
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The role of TGF-beta 1 in hydrogen peroxide-induced senescence-like morphogenesis has been described. The aim of this work was to investigate whether TGF-beta 1-independent changes in protein synthesis are involved in this morphogenesis and to study possible mechanisms occurring earlier than TGF-beta 1 overexpression. Among the multiple TGF-beta 1-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 beta 1 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-beta 1 signaling pathways. (c) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:1732 / 1751
页数:20
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