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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.
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页码:1732 / 1751
页数:20
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