Nitric oxide attenutates NMDA receptor-induced neuronal cell death independent of their intrinsic nitrosative abilities

A. S. Vidwans, S. Kim, D. O. Coffin, D. A. Wink, S. J. Hewett

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Nitric oxide (NO) has been implicated both in the pathogenesis of and the protection from NMDA-receptor mediated neuronal injury. This apparent paradox has been attributed to alternate redox states of NO, whereby depending on the redox milieu, NO can be neuroprotective via nitrosation chemistry (donation of a nitrosonium ion, NO+) or react with superoxide to form secondary toxic species. We now report that nitrosation is not a prerequisite for inhibition of NMDA toxicity. Brief intense exposure of murine mixed cortical cell cultures to NMDA (200 mM; 5 min) results in 60-80% neuronal cell death within 24 hr. Freshly prepared Dea/NO, Papa/NO and Sper/NO, NONOate-type NO donors, as well as, the S-nitrosothiols GSNO and SNAP (30-1000 mM), when given at the same time as NMDA, concentration-dependently decreased neuronal injury as assessed by a reduction in the amount of LDH released into the extracellular medium. The protection was lost when the donors were allowed to decompose 24 hr prior to experimentation. Electrochemical measurements of NO via an NO-sensitive electrode demonstrated that neuroprotective concentration of all donors, including SNAP and GSNO, produced appreciable amounts of NO over the 5 min time frame. Determination of the formation of NO+ equivalents, as assessed by nitrosation of 2,3 diaminonapthylene, revealed little or no observable nitrosation by SPER/NO and GSNO with significant nitrosation observed for all other donors, thus suggesting that the extent of nitrosation does not predict nor can it account for the protection of NO donors against NMDA toxicity.

Original languageEnglish (US)
Pages (from-to)165A
JournalJournal of Investigative Medicine
Volume47
Issue number2
StatePublished - Feb 1999
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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