Skip Navigation

Cardiovascular Research 2001 49(4):798-807; doi:10.1016/S0008-6363(00)00307-2
© 2001 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 ISI Web of Science
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 Search for citing articles in:
ISI Web of Science (72)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Mihm, M. J.
Right arrow Articles by Bauer, J. A.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Mihm, M. J.
Right arrow Articles by Bauer, J. A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2001, European Society of Cardiology

Peroxynitrite induced nitration and inactivation of myofibrillar creatine kinase in experimental heart failure

Michael J. Mihm, Christen M. Coyle, Brandon L. Schanbacher, David M. Weinstein and John Anthony Bauer*

Division of Pharmacology/College of Pharmacy and OSU Heart and Lung Research Institute The Ohio State University, 412 Riffe Building, 500 West Twelfth Street, Columbus, OH 43210, USA

* Corresponding author. Tel.: +1-614-292-1614; fax: +1-614-292-9083 bauer.140{at}osu.edu

Objective: Oxidative stress is implicated in the initiation and progression of congestive heart failure, but the putative reactive species and cellular targets involved remain undefined. We have previously shown that peroxynitrite (ONOO–, an aggressive biological oxidant and nitrating agent) potently inhibits myofibrillar creatine kinase (MM-CK), a critical controller of contractility known to be impaired during heart failure. Here we hypothesized that nitration and inhibition of MM-CK participate in cardiac failure in vivo. Methods: Heart failure was induced in rats by myocardial infarction (left coronary artery ligation) and confirmed by histological analysis at 8 weeks postinfarct (1.3±1.4 vs. 37.7±3.2% left ventricular circumference; sham control vs. CHF, n = 10 each). Results: Immunohistochemistry demonstrated significantly increased protein nitration in failing myocardium compared to control (optical density: 0.58±0.06 vs. 0.93±0.09, sham vs. CHF, P<0.05). Significant decreases in MM-CK activity and content were observed in failing hearts (MM-CK kcat: 6.0±0.4 vs. 3.0±0.3 µmol/nM M-CK/min, P<0.05; 6.8±1.3 vs. 4.7±1.2% myofibrillar protein, P<0.05), with no change in myosin ATPase activity. In separate experiments, isolated rat cardiac myofibrils were exposed to ONOO– (2–250 µM) and enzyme studies were conducted. Identical to in vivo studies, selective reductions in MM-CK were observed at ONOO– concentrations as low as 2 µM (IC50=92.5±6.0 µM); myosin ATPase was unaffected with ONOO– concentrations as high as 250 µM. Concentration dependent nitration of MM-CK occurred and extent of nitration was statistically correlated to extent of CK inhibition (P<0.001). Immunoprecipitation of MM-CK from failing left ventricle yielded significant evidence of tyrosine nitration. Conclusion: These data demonstrate that cardiac ONOO– formation and perturbation of myofibrillar energetic controllers occur during experimental heart failure; MM-CK may be a critical cellular target in this setting.

KEYWORDS Contractile function; Free radicals; Heart failure; Infarction; Nitric oxide


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
 ThoraxHome page
E Barreiro, R Rabinovich, J Marin-Corral, J A Barbera, J Gea, and J Roca
Chronic endurance exercise induces quadriceps nitrosative stress in patients with severe COPD
Thorax, January 1, 2009; 64(1): 13 - 19.
[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.