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Journal of Biochemistry Advance Access originally published online on May 18, 2009
Journal of Biochemistry 2009 146(3):307-315; doi:10.1093/jb/mvp070
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© The Authors 2009. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved

Nestin Serves as a Prosurvival Determinant that is Linked to the Cytoprotective Effect of Epidermal Growth Factor in Rat Vascular Smooth Muscle Cells

Yuan-Li Huang1,*, Ching-Ming Wu1,2,*, Guey-Yueh Shi3,4,*, Georgiana Cho-Chen Wu1, Hsinyu Lee5, Meei-Jyh Jiang2, Hua-Lin Wu3,4 and Hsi-Yuan Yang1,{dagger},{ddagger}

1Institute of Molecular and Cellular Biology, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 106; 2Department of Cell Biology and Anatomy, College of Medicine; 3Department of Biochemistry and Molecular Biology; 4Cardiovascular Research Center, National Cheng Kung University, No. 1, University Road, Tainan 701; and 5Institute of Zoology, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan

{ddagger}To whom correspondence should be addressed. Fax: +886-2-33662478, E-mail: hyhy{at}ntu.edu.tw

Received April 14, 2009; Accepted April 16, 2009


  Abstract

Nestin is an intermediate filament protein mainly expressed in muscle and neural progenitors. Recently, we reported that nestin is expressed in rat vascular smooth muscle cells (VSMCs), disappears after serum-deprivation and then is re-expressed again following EGF stimulation. As the function of nestin in VSMCs remains unknown, its anti-apoptotic function was investigated in this study. We first showed that cell viability of nestin-depleted cells following H2O2 treatments decreased by nestin RNAi. Further DNA laddering analysis and flow cytometry results demonstrated that this loss of cell viability was mediated through apoptosis. In addition, caspase-9, caspase-3 and PARP were activated in nestin-depleted VSMCs following H2O2 treatments, indicating that nestin has an upstream inhibitory effect on caspase activation. It is well known that EGF serves as a survival factor in rat VSMCs. Here, we show that the cytoprotective effect of EGF was prevented by nestin RNAi. In addition, the inhibition of Cdk5 prevented Bcl-2 phosphorylation and enhanced H2O2-induced caspase-3 activation as well as subsequent DNA fragmentation. Taken together, these results provide evidence for another cytoprotective role of EGF in that it is mediated through its stimulation of nestin expression which leads to the prevention of caspase activation by Cdk-5-induced Bcl-2 phosphorylation in rat VSMCs.

Key Words: nestin, apoptosis, EGF, caspase, CDK5, vascular smooth muscle cells

Abbreviations: CNS, central nervous system; IF, intermediated filament; VSMCs, vascular smooth muscle cells; EGF, epidermal growth factor; RNAi, RNA interference

*These authors are equal contributors to this work.

{dagger}Present address: Institute of Molecular and Cellular Biology, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan.


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