NEUROTOXICITY OF CYSTEINE - INTERACTION WITH GLUTAMATE

Citation
M. Pukasundvall et al., NEUROTOXICITY OF CYSTEINE - INTERACTION WITH GLUTAMATE, Brain research, 705(1-2), 1995, pp. 65-70
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences
Journal title
ISSN journal
0006-8993
Volume
705
Issue
1-2
Year of publication
1995
Pages
65 - 70
Database
ISI
SICI code
0006-8993(1995)705:1-2<65:NOC-IW>2.0.ZU;2-D
Abstract
L-Cysteine produces excitotoxic brain damage but its chemical structur e differs from that of other excitotoxins. Although it is an NMDA mime tic, its mode of action is complex and may encompass antiexcitotoxic c omponents. The purpose of the present study was to investigate whether cysteine kills neurons by potentiating the effects of glutamate and/o r by releasing glutamate. In primary cultures of cortical neurons, 24 h of exposure to glutamate caused a concentration-dependent, dizocilpi ne-sensitive cell death as measured by release of lactate dehydrogenas e. Cysteine was also toxic but higher concentrations were required. In addition, N-acetylcysteine produced mild toxicity at 1 mM. There was no general potentiation between either glutamate and cysteine or gluta mate and N-acetylcysteine although some combinations acted synergistic ally. In no case did the thiols inhibit glutamate toxicity. The intera ction between glutamate and cysteine toxicity was also assessed in the immature rat arcuate nucleus in vivo. When given at a dose (0.5 mg/g) that did not cause any toxicity per se, cysteine enhanced the toxicit y of glutamate (0.3-0.8 mg/g). Cortical microdialysis was carried out in anesthetized rats (8-10 days old) administered a toxic dose of cyst eine (1 mg/g). The levels of taurine were elevated 15-fold, phosphoeth anolamine 3-fold and alanine 2-fold. Despite the observation that glut amine decreased markedly and rapidly, there was only a delayed doublin g of glutamate concentrations. It is therefore unlikely that cysteine induces neurotoxicity by releasing glutamate. Taken together, the resu lts suggest that there is a synergistic effect between cysteine and gl utamate. Speculatively, this potentiation may be produced by reduction by cysteine of the redox site of the glutamate-activated NMDA recepto r-ionophore complex.