NDLI: Superoxide and peroxynitrite generation from inducible nitric oxide synthase in macrophages.

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Superoxide and peroxynitrite generation from inducible nitric oxide synthase in macrophages.

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Superoxide and peroxynitrite generation from inducible nitric oxide synthase in macrophages.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Xia, Y. Zweier, J. L.
Description	Author Affiliation: Xia Y ( Molecular and Cellular Biophysics Laboratories, Department of Medicine, Division of Cardiology, The Johns Hopkins University School of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, MD 21224, USA.);
Abstract	Superoxide (O-2) and nitric oxide (NO) act to kill invading microbes in phagocytes. In macrophages NO is synthesized by inducible nitric oxide synthase (iNOS, NOS 2) from L-arginine (L-Arg) and oxygen; however, O-2 was thought to be produced mainly by NADPH oxidase. Electron paramagnetic resonance (EPR) spin trapping experiments performed in murine macrophages demonstrate a novel pathway of O-2 generation. It was observed that depletion of cytosolic L-Arg triggers O-2 generation from iNOS. This iNOS-mediated O-2 generation was blocked by the NOS inhibitor N-nitro-L-arginine methyl ester or by L-Arg, but not by the noninhibitory enantiomer N-nitro-D-arginine methyl ester. In L-Arg-depleted macrophages iNOS generates both O-2 and NO that interact to form the potent oxidant peroxynitrite (ONOO-), which was detected by luminol luminescence and whose formation was blocked by superoxide dismutase, urate, or L-Arg. This iNOS-derived ONOO- resulted in nitrotyrosine formation, and this was inhibited by iNOS blockade. iNOS-mediated O-2 and ONOO- increased the antibacterial activity of macrophages. Thus, with reduced L-Arg availability iNOS produces O-2 and ONOO- that modulate macrophage function. Due to the existence of L-Arg depletion in inflammation, iNOS-mediated O-2 and ONOO- may occur and contribute to cytostatic/cytotoxic actions of macrophages.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	13
Volume Number	94
Language	English
Publisher	National Academy of Sciences
Publisher Date	1997-07-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Macrophages Metabolism Nitrates Nitric Oxide Synthase Superoxides Animals Cell Line Chromatography, High Pressure Liquid Electron Spin Resonance Spectroscopy Mice Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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