Nitric Oxide Activation of Poly(ADP-Ribose) Synthetase in Neurotoxicity

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Abstract
Poly(adenosine 5′-diphosphoribose) synthetase (PARS) is a nuclear enzyme which, when activated by DNA strand breaks, adds up to 100 adenosine 5′-diphosphoribose (ADP-ribose) units to nuclear proteins such as histones and PARS itself. This activation can lead to cell death through depletion of β-nicotinamide adenine dinucleotide (the source of ADP-ribose) and adenosine triphosphate. Nitric oxide (NO) stimulated ADP-ribosylation of PARS in rat brain. Benzamide and other derivatives, which inhibit PARS, blocked N -methyl-D-aspartate- and NO-mediated neurotoxicity with relative potencies paralleling their ability to inhibit PARS. Thus, NO appeared to elicit neurotoxicity by activating PARS.

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