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Kainic acid‐induced neuronal cell death in cerebellar granule cells is not prevented by caspase inhibitors
Author(s) -
Verdaguer Ester,
GarcíaJordà Elvira,
Jiménez Andrés,
Stranges Alessandra,
Sureda Francesc X,
Canudas Anna M,
Escubedo Elena,
Camarasa Jordi,
Pallàs Mercè,
Camins Antoni
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704581
Subject(s) - kainic acid , ampa receptor , nbqx , apoptosis , excitotoxicity , programmed cell death , biology , glutamate receptor , granule cell , calcium in biology , colchicine , caspase , microbiology and biotechnology , chemistry , intracellular , endocrinology , receptor , biochemistry , hippocampal formation , dentate gyrus , genetics
We examined the role of non‐NMDA receptors in kainic acid (KA)‐induced apoptosis in cultures of rat cerebellar granule cells (CGCs). KA (1 – 500 μ M ) induced cell death in a concentration‐dependent manner, which was prevented by NBQX and GYKI 52466, non‐NMDA receptor antagonists. Moreover, AMPA blocked KA‐induced excitotoxicity, through desensitization of AMPA receptors. Similarly, KA raised the intracellular calcium concentration of CGCs, which was inhibited by NBQX and GYKI 52466. Again, AMPA (100 μ M ) abolished the KA (100 μ M )‐induced increase in intracellular calcium concentration. KA‐induced cell death in CGCs had apoptotic features, which were determined morphologically, by DNA fragmentation, and by expression of the prostate apoptosis response‐4 protein (Par‐4). KA (500 μ M ) slightly (18%) increased caspase‐3 activity, which was strongly enhanced by colchicine (1 μ M ), an apoptotic stimulus. However, neither Z ‐VAD.fmk, a pan‐caspase inhibitor, nor the more specific caspase‐3 inhibitor, Ac‐DEVD‐CHO, prevented KA‐induced cell death or apoptosis. In contrast, both drugs inhibited colchicine‐induced apoptosis. The calpain inhibitor ALLN had no effect on KA or colchicine‐induced neurotoxicity. Our findings indicate that colchicine‐induced apoptosis in CGCs is mediated by caspase‐3 activation, unlike KA‐induced apoptosis.British Journal of Pharmacology (2002) 135 , 1297–1307; doi: 10.1038/sj.bjp.0704581