NITRIC-OXIDE ACTIVATION OF POLY(ADP-RIBOSE) SYNTHETASE IN NEUROTOXICITY

被引：1025

作者：

ZHANG, J

DAWSON, VL

DAWSON, TM

SNYDER, SH

机构：

[1] JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205

[2] NIDA,ADDICT RES CTR,MOLEC NEUROPSYCHIAT SECT,BALTIMORE,MD 21224

[3] JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL & MOLEC SCI,BALTIMORE,MD 21205

[4] JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21205

[5] JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205

来源：

SCIENCE | 1994年 / 263卷 / 5147期

关键词：

D O I：

10.1126/science.8080500

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：687 / 689

页数：3

共 34 条

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