The role of nitric oxide and PARP in neuronal cell death

Mika Shimoji, Valina L. Dawson

Research output: Chapter in Book/Report/Conference proceedingChapter


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).

Original languageEnglish (US)
Title of host publicationNeurodegenerative Diseases
Subtitle of host publicationNeurobiology, Pathogenesis and Therapeutics
PublisherCambridge University Press
Number of pages11
ISBN (Electronic)9780511544873
ISBN (Print)052181166X, 9780521811668
StatePublished - Jan 1 2005

ASJC Scopus subject areas

  • Medicine(all)


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