The role of nitric oxide and PARP in neuronal cell death

doi:10.1017/CBO9780511544873.013

12 - The role of nitric oxide and PARP in neuronal cell death

from Part I - Basic aspects of neurodegeneration

Published online by Cambridge University Press: 04 August 2010

Anthony E. Lang and

Valina L. Dawson and

M. Flint Beal: Affiliation:
Cornell University, New York
Anthony E. Lang: Affiliation:
University of Toronto
Albert C. Ludolph: Affiliation:
Universität Ulm, Germany
Mika Shimoji: Affiliation:
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Valina L. Dawson: Affiliation:
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Ted M. Dawson: Affiliation:
Department of Neurology, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Pathol 2-210, Baltimore, MD 21205, USA

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Summary

Nitric oxide

Nitric oxide (NO) is a novel neuronal messenger molecule that is not confined to the synaptic cleft and can mediate rapid signaling by diffusing freely in three dimensions to act throughout local regions of neural tissue (Dawson & Dawson, 1998). NO can be generated in most tissues in the body and was first identified as endothelium-derived relaxing factor (EDRF) in blood vessels where it is the major regulator of vascular tone (Furchgott & Zawadzki, 1980; Palmer et al., 1987; Kilbourn & Belloni, 1990; Ignarro, 1991). NO is produced by the enzymatic conversion of L-arginine to L-citrulline by nitric oxide synthase (NOS). In the NO biosynthetic scheme, L-arginine is first oxygenated to the intermediate NG-hydroxy-L-arginine, which is then oxygenated to produce NO and L-citrulline. NO has a short half-life due to the pervasive action of superoxide (Palmer et al., 1987). There are three isoforms of NOS. Two isoforms are expressed constitutively (neuronal; nNOS, endothelial; eNOS) and one that expressed only after induction (inducible; iNOS) (Fujisawa et al., 1994; Chartrain et al., 1994; Marsden et al., 1993). Both the constitutive and inducible forms are tetrahydrobiopterin (BH4) dependent (Tayeh & Marletta, 1989; Kwon et al., 1989). The constitutive isoforms, nNOS and eNOS are Ca2+/calmodulin regulated and thus NO generation is dependent on calcium signaling events. However, iNOS is Ca2+/calmodulin independent and therefore NO is generated from iNOS upon protein expression. NO generation from iNOS is regulated by the duration of mRNA expression for iNOS (Dawson & Dawson, 1998).

Type: Chapter
Information: Neurodegenerative Diseases
Neurobiology, Pathogenesis and Therapeutics
, pp. 146 - 156

DOI: https://doi.org/10.1017/CBO9780511544873.013 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2005

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