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 beta-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.
Publication types
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, P.H.S.
MeSH terms
- Animals
- Benzamides / pharmacology
- Brain / cytology
- Brain / drug effects
- Brain / enzymology
- Cell Death / drug effects
- Cell Line
- Cells, Cultured
- Cerebral Cortex / cytology
- Cerebral Cortex / drug effects
- Cerebral Cortex / enzymology
- DNA Damage
- Enzyme Activation
- Humans
- N-Methylaspartate / toxicity*
- Neurons / cytology
- Neurons / drug effects*
- Neurons / enzymology
- Nitric Oxide / toxicity*
- Poly(ADP-ribose) Polymerase Inhibitors
- Poly(ADP-ribose) Polymerases / metabolism*
- Rats
- Rats, Sprague-Dawley
Substances
- Benzamides
- Poly(ADP-ribose) Polymerase Inhibitors
- Nitric Oxide
- N-Methylaspartate
- benzamide
- Poly(ADP-ribose) Polymerases