Skip Navigation

Cardiovascular Research 1999 42(3):805-813; doi:10.1016/S0008-6363(98)00342-3
© 1999 by European Society of Cardiology
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
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 Li, D.
Right arrow Articles by L. Mehta, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, D.
Right arrow Articles by L. Mehta, J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 1999, European Society of Cardiology

Tumor necrosis factor-{alpha} enhances hypoxia–reoxygenation-mediated apoptosis in cultured human coronary artery endothelial cells: critical role of protein kinase C

Dayuan Li, Baichun Yang and Jawahar L. Mehta*

Department of Medicine, University of Florida College of Medicine, 1600 Archer Rd., P.O. Box 100277 JHMHC, Gainesville FL 32610, USA

* Corresponding author. Tel.: +1-352-379-4160; fax: +1-352-379-4161. E-mail address: mehta@medmac.ufl.edu (J.L. Mehta)

Background: Ischemia and tumor necrosis factor-{alpha} (TNF{alpha}) released during ischemia both cause apoptosis and necrosis of myocardial tissues. Since endothelium may be critically important in determination of cardiac function, we examined the interaction between TNF{alpha} and hypoxia–reoxygenation with regard to induction of apoptosis and underlying signaling pathway in cultured human coronary artery endothelial cells (HCAECs). Methods and results: HCAECs were cultured and exposed to hypoxia alone, hypoxia–reoxygenation, TNF{alpha} alone, TNF{alpha} plus hypoxia–reoxygenation, or TNF{alpha} only during the period of reoxygenation. Apoptosis was evaluated by transmission electron microscopy, DNA nick-end labeling and DNA laddering. Hypoxia alone caused modest time-dependent apoptosis of cultured HCAECs, and reoxygenation increased the number of apoptotic cells (P<0.01 vs. hypoxia alone). TNF{alpha} induced concentration-dependent apoptosis, and enhanced reoxygenation-mediated apoptosis in cultured HCAECs (P<0.01 vs. hypoxia–reoxygenation alone). As expected, monoclonal antibody to TNF{alpha} significantly blocked the pro-apoptotic effect of TNF{alpha}-induced apoptosis (P<0.01). TNF{alpha}-induced apoptosis was found to be associated with marked activation of protein kinase C (PKC), and pretreatment of cells with a specific PKC inhibitor markedly reduced TNF{alpha}-mediated PKC activity and apoptosis. Conclusion: These observations indicate that hypoxia alone causes modest apoptosis, reoxygenation increases apoptosis beyond that caused by hypoxia in cultured HCAECs. TNF{alpha} alone causes apoptosis, and further enhances apoptosis caused by hypoxia–reoxygenation. The activation of PKC plays a critical role in TNF{alpha}-induced apoptosis of cultured HCAECs.

KEYWORDS Apoptosis; Endothelial cell; Hypoxia; Reoxygenation; Tumor necrosis factor-{alpha}


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


This article has been cited by other articles:


Home page
 Biol. Reprod.Home page
C. Paul, S. Teng, and P. T.K. Saunders
A Single, Mild, Transient Scrotal Heat Stress Causes Hypoxia and Oxidative Stress in Mouse Testes, Which Induces Germ Cell Death
Biol Reprod, May 1, 2009; 80(5): 913 - 919.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
S. S. Palaniyandi, L. Sun, J. C. B. Ferreira, and D. Mochly-Rosen
Protein kinase C in heart failure: a therapeutic target?
Cardiovasc Res, May 1, 2009; 82(2): 229 - 239.
[Abstract] [Full Text] [PDF]


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.