Skip Navigation



Journal of Biochemistry Advance Access published online on May 18, 2009
Journal of Biochemistry, doi:10.1093/jb/mvp070
This Article
Right arrow Advance Access manuscript (PDF)
Right arrow All Versions of this Article:
146/3/307    most recent
mvp070v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Huang, Y.-L.
Right arrow Articles by Yang, H.-Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Huang, Y.-L.
Right arrow Articles by Yang, H.-Y.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 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,{dagger} and Hsi-Yuan Yang1,{dagger}

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

{dagger}Corresponding authors. Fax: +886-2-33662478, E-mail: hyhy{at}ntu.edu.tw (Hsi-Yuan Yang)

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. Herein, 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

*These authors contributed equally to this work.

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


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.