title: 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.affiliation: Second Department of Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Natsuya
authors.initials: N
authors.lastname: Keira
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tatsumi
authors.forename: Satoaki
authors.initials: S
authors.lastname: Matoba
authors.forename: Jun
authors.initials: J
authors.lastname: Shiraishi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamanaka
authors.forename: Kazuko
authors.initials: K
authors.lastname: Akashi
authors.forename: Miyuki
authors.initials: M
authors.lastname: Kobara
authors.forename: Jun
authors.initials: J
authors.lastname: Asayama
authors.forename: Shinji
authors.initials: S
authors.lastname: Fushiki
authors.forename: Henry
authors.initials: H
authors.lastname: Fliss
authors.forename: Masao
authors.initials: M
authors.lastname: Nakagawa
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D030421:Peroxynitrous Acid / Q000378:metabolism*; D051381:Rats
chemical_list: D016207:Cytokines; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat