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Apoptotic Cell Death and Caspase‐3 Activation Induced by N ‐Methyl‐ d ‐Aspartate Receptor Antagonists and Their Prevention by Insulin‐Like Growth Factor I
Author(s) -
Takadera Tsuneo,
Matsuda Ikumi,
Ohyashiki Takao
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0730548.x
Subject(s) - nmda receptor , programmed cell death , apoptosis , microbiology and biotechnology , biology , caspase , glutamate receptor , intracellular , caspase 3 , receptor , biochemistry
: The effect of N ‐methyl‐ d ‐aspartate (NMDA) receptor antagonists on cell viability was studied in rat primary cortical cells. NMDA antagonists [MK‐801 and 2‐amino‐5‐phosphonovalerate (APV)] induced cell shrinkage, nuclear condensation or fragmentation, and internucleosomal DNA fragmentation. Treatment of cells with MK‐801 (an NMDA antagonist) for 1‐2 days induced apoptotic cell death in a dose‐dependent manner (1 n M to 10 μ M ). NMDA (25 μ M ), however, inhibited the MK‐801 (0.1 μ M )‐induced apoptotic cell death. MK‐801 and APV decreased the concentration of intracellular calcium ion. Activation of caspase‐3 was accompanied by MK‐801‐induced cell death in a dose‐dependent manner, and an inhibitor of caspase‐3 reduced the cell death. Further, cycloheximide (0.2 μg/ml) completely protected the cells from MK‐801‐induced apoptotic cell death and caspase‐3 activation. Insulin‐like growth factor I completely attenuated MK‐801‐induced apoptotic cell death and caspase‐3 activation. These results demonstrated that the moderate NMDA receptor activation is probably involved in the survival signal of the neuron.