Skip Navigation

European Journal of Heart Failure 2003 5(2):121-129; doi:10.1016/S1388-9842(02)00254-4
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
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Sharov, V. G.
Right arrow Articles by Sabbah, H. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sharov, V. G.
Right arrow Articles by Sabbah, H. N.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2002 European Society of Cardiology

Hypoxia, angiotensin-II, and norepinephrine mediated apoptosis is stimulus specific in canine failed cardiomyocytes: a role for p38 MAPK, Fas-L and cyclin D1

Victor G. Sharov, Anastassia Todor, George Suzuki, Hideaki Morita, Elaine J. Tanhehco and Hani N. Sabbah*

Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute Detroit, MI 48202, USA

* Corresponding author. Cardiovascular Research, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, USA. Tel.: +1-313-916-7360; fax: +1-313-916-3001 E-mail address: hsabbah1{at}hfhs.org


  Abstract

Background: Apoptosis may contribute to the myocardial dysfunction associated with heart failure (HF). Activation of the p38 MAPK cascade can induce apoptosis in non-cardiac cells through increased expression of Fas-L, or through decreased expression of cyclin D1.

Aims: We tested the hypothesis that hypoxia (HX), angiotensin-II (A-II) and norepinephrine (NEPI) can mediate apoptosis by activating p38 MAPK, and thus initiating stimulus specific changes in Fas-L and cyclin D1 expression in failing cardiomyocytes.

Methods and results: Cardiomyocytes isolated from ten dogs with HF induced by coronary microembolizations were subjected to HX or A-II or NEPI with and without a p38 MAPK inhibitor (SB 203580). TUNEL staining for DNA fragmentation and Western blots for p38 MAPK, Fas-L and cyclin D1 detection were performed. HX-induced apoptosis was associated with increased Fas-L expression, A-II-induced apoptosis was associated with increased Fas-L and decreased cyclin D1 expression, and NEPI-induced apoptosis was associated with decreased cyclin D1 expression. Inhibition of p38 MAPK activity attenuated stress-induced apoptosis in all experiments and reversed changes in Fas-L and cyclin D1 expression.

Conclusions: HX, A-II and NEPI mediate apoptosis in failing cardiomyocytes via different effects on Fas-L and cyclin D1 expression. Inhibition of p38 MAPK reversed these effects, suggesting that apoptosis induced by HX, A-II and NEPI involves activation of p38 MAPK upstream from Fas-L and cyclin D1.

Key Words: Heart failure • p38 MAPK • Apoptosis • Fas-L • Cyclin D1

Received April 2, 2002; Revised July 9, 2002; Accepted September 17, 2002


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
 Am. J. Physiol. Heart Circ. Physiol.Home page
K.-i. Watanabe, M. Ma, K.-i. Hirabayashi, N. Gurusamy, P. T. Veeraveedu, P. Prakash, S. Zhang, A. J. Muslin, M. Kodama, and Y. Aizawa
Swimming stress in DN 14-3-3 mice triggers maladaptive cardiac remodeling: role of p38 MAPK
Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1269 - H1277.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
G. De Chiara, M. E. Marcocci, M. Torcia, M. Lucibello, P. Rosini, P. Bonini, Y. Higashimoto, G. Damonte, A. Armirotti, S. Amodei, et al.
Bcl-2 Phosphorylation by p38 MAPK: IDENTIFICATION OF TARGET SITES AND BIOLOGIC CONSEQUENCES
J. Biol. Chem., July 28, 2006; 281(30): 21353 - 21361.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. K. Kim, A. Pedram, M. Razandi, and E. R. Levin
Estrogen Prevents Cardiomyocyte Apoptosis through Inhibition of Reactive Oxygen Species and Differential Regulation of p38 Kinase Isoforms
J. Biol. Chem., March 10, 2006; 281(10): 6760 - 6767.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. A. Kaiser, O. F. Bueno, D. J. Lips, P. A. Doevendans, F. Jones, T. F. Kimball, and J. D. Molkentin
Targeted Inhibition of p38 Mitogen-activated Protein Kinase Antagonizes Cardiac Injury and Cell Death Following Ischemia-Reperfusion in Vivo
J. Biol. Chem., April 9, 2004; 279(15): 15524 - 15530.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
S. Zhang, J. Ren, C. E. Zhang, I. Treskov, Y. Wang, and A. J. Muslin
Role of 14-3-3-Mediated p38 Mitogen-Activated Protein Kinase Inhibition in Cardiac Myocyte Survival
Circ. Res., November 28, 2003; 93(11): 1026 - 1028.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
A. Gonzalez, M. A Fortuno, R. Querejeta, S. Ravassa, B. Lopez, N. Lopez, and J. Diez
Cardiomyocyte apoptosis in hypertensive cardiomyopathy
Cardiovasc Res, September 1, 2003; 59(3): 549 - 562.
[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.