Skip Navigation



Cardiovascular Research Advance Access [Accepted Manuscript] published online on October 30, 2007
Cardiovascular Research, doi:10.1093/cvr/cvm057
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
77/3/551    most recent
cvm057v2
cvm057v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
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 arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Cheng, W.-P.
Right arrow Articles by Shyu, K.-G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cheng, W.-P.
Right arrow Articles by Shyu, K.-G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

The Molecular Regulation of GADD153 in Apoptosis of Cultured Vascular Smooth Muscle Cells by Cyclic Mechanical Stretch

Wen-Pin Cheng1, Huei-Fong Hung2, Bao-Wei Wang2 and Kou-Gi Shyu1,2,

1 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
2 Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

Correspondence to Dr. Shyu, Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, 95 Wen-Chang Rd, Taipei 111, Taiwan Tel: 886-2-28332211; Fax: 886-2-28365775; E-mail: shyukg{at}ms12.hinet.net

Aim: The expression of GADD153 (growth arrest and DNA damage-inducible gene 153), an apoptosis-regulated gene, increases during endoplasmic reticulum (ER) stress. How mechanical stretch affects the regulation of GADD153 in vascular smooth muscle cells (VSMCs) during apoptosis is not fully understood. We aimed to test the hypothesis that mechanical stretch induces GADD153 expression in VSMCs undergoing apoptosis.

Methods: Rat VSMCs grown on a flexible membrane base were stretched by vacuum to 20% of maximum elongation, at 60 cycles/min. An in vivo model of aorta-caval shunt in adult rats was used to investigate GADD153 expression.

Results: Cyclic stretch significantly increased GADD153 protein and mRNA expression after 18 h of stretch. Addition of c-jun N-terminal kinase (JNK) inhibitor SP600125, JNK siRNA, tumor necrosis factor-{alpha} (TNF-{alpha}) and TNF-{alpha} receptor antibody 30 min before stretch inhibited the induction of GADD153 protein. Gel shift assay showed that DNA-binding activity of activating factor 1 (AP-1) increased after stretch. SP600125, JNK siRNA and TNF-{alpha} antibody abolished the binding activity induced by stretch. Stretch increased while GADD153-Mut plasmid, SP600125, and c-jun antibody abolished the promoter activity. Both conditioned media from stretched VSMCs and exogenous administration of TNF-{alpha} recombinant protein to the non-stretched VSMCs increased GADD153 protein expression similar to that seen after stretch. An in vivo model of aorta-caval shunt in adult rats also demonstrated the increased GADD153 protein expression in the aorta.

Conclusions: Cyclic stretch enhanced GADD153 expression in cultured rat VSMCs. The stretch-induced GADD153 is mediated by TNF-{alpha}, at least in part, through the JNK and AP-1 pathway. These findings suggest that GADD153 plays a role in stretched-induced VSMC apoptosis.

Time for primary review: 25


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.