Apoptosis and necrosis: Two distinct events induced, respectively, by mild and intense insults with N-methyl-D-aspartate or nitric oxide/superoxide in cortical cell cultures

Emanuela Bonfoco, Dimitri Krainc, Maria Ankarcrona, Pierluigi Nicotera, Stuart A. Lipton*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1836 Scopus citations

Abstract

N-Methyl-D-aspartate (NMDA) receptor-mediated neurotoxicity may depend, in part, on the generation of nitric oxide (NO.) and superoxide anion (O2/.- ), which react to form peroxynitrite (OONO-). This form of neurotoxicity is thought to contribute to a final common pathway of injury in a wide variety of acute and chronic neurologic disorders, including focal ischemia, trauma, epilepsy, Huntington disease, Alzheimer disease, amyotrophic lateral sclerosis, AIDS dementia, and other neurodegenerative diseases. Here, we report that exposure of cortical neurons to relatively short durations or low concentrations of NMDA, S-nitrosocysteine, or 3-morpholinosydnonimine, which generate low levels of peroxynitrite, induces a delayed form of neurotoxicity predominated by apoptotic features. Pretreatment with superoxide dismutase and catalase to scavenge O2/.- partially prevents the apoptotic process triggered by S-nitrosocysteine or 3-morpholinosydnonimine. In contrast, intense exposure to high concentrations of NMDA or peroxynitrite induces necrotic cell damage characterized by acute swelling and lysis, which cannot be ameliorated by superoxide dismutase and catalase. Thus, depending on the intensity of the initial insult, NMDA or nitric oxide/superoxide can result in either apoptotic or necrotic neuronal cell damage.

Original languageEnglish (US)
Pages (from-to)7162-7166
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number16
DOIs
StatePublished - Aug 1 1995

Keywords

  • cortical neurons
  • excitotoxicity
  • peroxynitrite

ASJC Scopus subject areas

  • General

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