Skip Navigation

Cardiovascular Research 2004 62(3):578-586; doi:10.1016/j.cardiores.2004.01.031
© 2004 by European Society of Cardiology
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
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 arrowRequest Permissions
Google Scholar
Right arrow Articles by Sasaki, S.
Right arrow Articles by Okumura, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sasaki, S.
Right arrow Articles by Okumura, K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2004, European Society of Cardiology

Tumor necrosis factor {alpha} as an endogenous stimulator for circulating coupling factor 6

Satoko Sasakia, Tomohiro Osanai*,a, Hirofumi Tomitaa, Toshiro Matsunagaa, Koji Magotab and Ken Okumuraa

aThe Second Department of Internal Medicine, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan
bDaiichi Suntory Biomedical Research CO., LTD., Osaka 618-8513, Japan

* Corresponding author. Tel.: +81-172-39-5057; fax: +81-172-35-9190. Email address: osanait{at}cc.hirosaki-u.ac.jp

Objective: We recently showed that mitochondrial coupling factor 6 (CF6) is present as a pressor substance and a prostacyclin inhibitor in systemic circulation. However, the regulation mechanism for circulating CF6 is unknown. We investigated the role of tumor necrosis factor-{alpha} (TNF-{alpha}) in the generation and release of CF6. Methods and results: We used two kinds of cells, human umbilical vein endothelial cells (HUVEC) and ECV-304. The concentration of CF6 in the medium increased with time in both ECV-304 and HUVEC. Treatment of ECV-304 and HUVEC with TNF-{alpha} enhanced the release of CF6 in a dose-dependent manner concomitantly with the decrease in CF6 content in the mitochondria at 24 h. The released CF6 was characterized to be an active full-length peptide by Western blot. The ratio of CF6 to GAPDH mRNA, measured by real-time polymerase chain reaction, was 1.7 fold increased at 1 h after exposure to TNF-{alpha} in ECV-304 and HUVEC. This enhanced gene expression and release was blocked or suppressed by 70% by stable transfection of dominant negative mutant I{kappa}B kinase {alpha} whose efficacy was confirmed by blockade of translocation of NF-{kappa}B p65 protein and of degradation of I{kappa}B{alpha} protein. Flow cytometry analysis revealed that the cell surface-associated CF6 was significantly increased at 24 h after TNF-{alpha} in a dose-dependent manner. Conclusions: TNF-{alpha} stimulates the gene expression of CF6 via activation of NF-{kappa}B signaling pathway, and promotes the release of CF6 from ECV-304 and HUVEC.

KEYWORDS Prostacyclin; Coupling factor 6; Tumor necrosis factor {alpha}; Vascular endothelial cells; Nuclear factor {kappa}B

Time for primary review 16 days


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.