Requirement for superoxide in excitotoxic cell death.

Published

Journal Article

We tested the pathogenic role of O2-) radicals in excitotoxic injury. Inactivation of the TCA cycle enzyme, aconitase, was used as a marker of intracellular O2- levels, and a porphyrin SOD mimetic was used to scavenge O2-. The selective, reversible, and SOD-sensitive inactivation of aconitase by known O2- generators was used to validate aconitase activity as a marker of O2- generation. Treatment of rat cortical cultures with NMDA, KA, or the intracellular O2- generator PQ2+ produced a selective and reversible inactivation of aconitase, which closely correlated with subsequent cell death produced by these agents. The SOD mimetic, but not its less active congener, attenuated both aconitase inactivation and cell death produced by NMDA, KA, and PQ2+. These results provide direct evidence implicating O2(-) generation in the pathway to excitotoxic injury.

Full Text

Duke Authors

Cited Authors

  • Patel, M; Day, BJ; Crapo, JD; Fridovich, I; McNamara, JO

Published Date

  • February 1996

Published In

Volume / Issue

  • 16 / 2

Start / End Page

  • 345 - 355

PubMed ID

  • 8789949

Pubmed Central ID

  • 8789949

International Standard Serial Number (ISSN)

  • 0896-6273

Digital Object Identifier (DOI)

  • 10.1016/s0896-6273(00)80052-5

Language

  • eng

Conference Location

  • United States