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| NITRIC-OXIDE ACTIVATION OF POLY(ADP-RIBOSE) SYNTHETASE IN NEUROTOXICITY |
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| Author(s): ZHANG J, DAWSON VL, DAWSON TM, SNYDER SH |
| Source: SCIENCE Volume: 263 Issue: 5147 Pages: 687-689 Published: FEB 4 1994 |
| Times Cited: 857 References: 34 |
| 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. |
| Document Type: Article |
| Language: English |
Addresses:
1. JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROSCI, BALTIMORE, MD 21205 USA
2. NIDA, ADDICT RES CTR, MOLEC NEUROPSYCHIAT SECT, BALTIMORE, MD 21224 USA
3. JOHNS HOPKINS UNIV, SCH MED, DEPT PHARMACOL & MOLEC SCI, BALTIMORE, MD 21205 USA
4. JOHNS HOPKINS UNIV, SCH MED, DEPT PSYCHIAT & BEHAV SCI, BALTIMORE, MD 21205 USA
5. JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROL, BALTIMORE, MD 21205 USA |
| Publisher: AMER ASSOC ADVANCEMENT SCIENCE, 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: MU964 |
| ISSN: 0036-8075 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |