OXYGEN FREE-RADICALS REGULATE NMDA RECEPTOR FUNCTION VIA A REDOX MODULATORY SITE

被引：184

作者：

AIZENMAN, E ^{[1
]}

HARTNETT, KA ^{[1
]}

REYNOLDS, IJ ^{[1
]}

机构：

[1] UNIV PITTSBURGH,SCH MED,DEPT PHARMACOL,PITTSBURGH,PA 15261

来源：

NEURON | 1990年 / 5卷 / 06期

关键词：

D O I：

10.1016/0896-6273(90)90343-E

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

A nobel modulatory site on the N-methyl-D-aspartate (NMDA) receptor that is sensitive to sulfhydryl redox reagents was recently described. Here we report that this redox modulatory site is susceptible to oxidation by reactive oxygen species endogenous to the CNS. Oxygen free radicals generated by xanthine and xanthine oxidase were observed to decrease NMDA-induced changes in intracellular free Ca2+ concentrations and NMDA-evoked cation currents in cortical neurons in culture. Additionally, a sublethal production of free radicals by xanthine and xanthine oxidase reversed a dithiothreitol-induced enhancement of NMDA-mediated neurotoxicity in vitro. These results show that NMDA receptor function is modulated at its redox site by endogenous substances that normally accompany tissue reperfusion following an ischemic event. This novel mechanism for NMDA receptor regulation may have profound implications in the outcome of glutamate neurotoxicity in vivo.

引用

页码：841 / 846

页数：6

共 36 条

[1] RESPONSES MEDIATED BY EXCITATORY AMINO-ACID RECEPTORS IN SOLITARY RETINAL GANGLION-CELLS FROM RAT [J].

AIZENMAN, E ;

FROSCH, MP ;

LIPTON, SA .

JOURNAL OF PHYSIOLOGY-LONDON, 1988, 396 :75-91

[2] SELECTIVE MODULATION OF NMDA RESPONSES BY REDUCTION AND OXIDATION [J].

AIZENMAN, E ;

LIPTON, SA ;

LORING, RH .

NEURON, 1989, 2 (03) :1257-1263

[3] THE EXCITATORY AMINO-ACID ANTAGONIST KYNURENIC ACID ADMINISTERED AFTER HYPOXIC-ISCHEMIA IN NEONATAL RATS OFFERS NEUROPROTECTION [J].

ANDINE, P ;

LEHMANN, A ;

ELLREN, K ;

WENNBERG, E ;

KJELLMER, I ;

NIELSEN, T ;

HAGBERG, H .

NEUROSCIENCE LETTERS, 1988, 90 (1-2) :208-212

[4]

BENEVISTE H, 1984, J NEUROCHEM, V43, P1369

[5] IDENTIFICATION OF HYPOXANTHINE TRANSPORT AND XANTHINE-OXIDASE ACTIVITY IN BRAIN CAPILLARIES [J].

BETZ, AL .

JOURNAL OF NEUROCHEMISTRY, 1985, 44 (02) :574-579

[6] CENTRAL NERVOUS-SYSTEM TRAUMA AND STROKE .1. BIOCHEMICAL CONSIDERATIONS FOR OXYGEN RADICAL FORMATION AND LIPID-PEROXIDATION [J].

BRAUGHLER, JM ;

HALL, ED .

FREE RADICAL BIOLOGY AND MEDICINE, 1989, 6 (03) :289-301

[7] EVIDENCE OF DIRECT TOXIC EFFECTS OF FREE-RADICALS ON THE MYOCARDIUM [J].

BURTON, KP .

FREE RADICAL BIOLOGY AND MEDICINE, 1988, 4 (01) :15-24

[8] OXYGEN FREE-RADICAL INVOLVEMENT IN ISCHEMIA AND REPERFUSION INJURY TO BRAIN [J].

CAO, W ;

CARNEY, JM ;

DUCHON, A ;

FLOYD, RA ;

CHEVION, M .

NEUROSCIENCE LETTERS, 1988, 88 (02) :233-238

[9] GLUTAMATE NEUROTOXICITY AND DISEASES OF THE NERVOUS-SYSTEM [J].

CHOI, DW .

NEURON, 1988, 1 (08) :623-634

[10] NEUROTRANSMITTER AMINO-ACIDS IN THE CNS .1. REGIONAL CHANGES IN AMINO-ACID LEVELS IN RAT-BRAIN DURING ISCHEMIA AND REPERFUSION [J].

ERECINSKA, M ;

NELSON, D ;

WILSON, DF ;

SILVER, IA .

BRAIN RESEARCH, 1984, 304 (01) :9-22

← 1 2 3 4 →