Author/Editor		Bonfoco, Emanuela; Krainc, Dimitri; Ankarcrona, Maria; Nicotera, Pierluigi; Lipton, Stuart A
Title		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
Type		članek
Source		Proc Natl Acad Sci U S A
Vol. and No.		Letnik 92, št. 16
Publication year		1995
Volume		str. 7162-6
Language		eng
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 scelerosis, 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.
Descriptors		ANIMALS APOPTOSIS CELLS, CULTURED CEREBRAL CORTEX CYSTEINE DNA FREE RADICALS KINETICS MOLSIDOMINE N-METHYLASPARTATE NECROSIS NEURONS NITRATES NITRIC OXIDE OXIDATIVE STRESS RATS SUPEROXIDE DISMUTASE SUPEROXIDES