Lethal effect of cytokine-induced nitric oxide and peroxynitrite on cultured rat cardiac myocytes.

Abstract

We examined the cytotoxic effect of iNOS-generated NO in cultured cardiac myocytes treated with IL-1 beta, IFN- gamma and LPS. Treatment of the myocytes with cytokines for 48 h resulted in a marked NO production, a significant decline in cellular ATP content, and a significant increase in myocyte death with morphological characteristics of necrosis. Moreover, immunohistochemical examination showed that the cytokines caused nitrotyrosine formation in the injured myocytes. Uric acid and L-cysteine which have the ability to quench peroxynitrite significantly attenuated these cytokine-induced effects, although they did not alter NO production or the decline in cellular ATP. These data suggest that NO production induced by cytokines can not only cause deleterious effects in the myocardial energy balance but also induce myocytes necrosis, through the formation of peroxynitrite.

• Authors: Natsuya Keira, Tetsuya Tatsumi, Satoaki Matoba, Jun Shiraishi, Satoshi Yamanaka, Kazuko Akashi, Miyuki Kobara, Jun Asayama, Shinji Fushiki, Henry Fliss, Masao Nakagawa
• Journal: Journal of molecular and cellular cardiology (J Mol Cell Cardiol) Vol. 34 Issue 5 Pg. 583-96 (May 2002) ISSN: 0022-2828 [Print] England
• PMID: 12056861 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2002 Academic Press.

Chemical References

• Cytokines
• Peroxynitrous Acid
• Nitric Oxide
• Adenosine Triphosphate
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type II
• Nos2 protein, rat

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Cell Death (drug effects)
• Cells, Cultured
• Cytokines (pharmacology)
• Energy Metabolism (drug effects)
• Muscle Fibers, Skeletal (metabolism)
• Myocardium (metabolism, pathology)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase (metabolism)
• Nitric Oxide Synthase Type II
• Peroxynitrous Acid (metabolism)
• Rats