Kainic acid-induced neuronal cell death in cerebellar granule cells is not prevented by caspase inhibitors

Verdaguer, E; Garcia-Jorda, E; Jimenez, A; Stranges, A; Sureda, FX; Canudas, AM; Escubedo, E; Camarasa, J; Pallas, M; Camins, A


1 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 mum) 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. 2 Similarly, KA raised the intracellular calcium concentration of CGCs, which was inhibited by NBQX and GYKI 52466. Again, AMPA (100 mum) abolished the KA (100 mum)-induced increase in intracellular calcium concentration. 3 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). 4 KA (500 mum) slightly (18%) increased caspase-3 activity, which was strongly enhanced by colchicine (1 mum), 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. 5 The calpain inhibitor ALLN had no effect on KA or colchicine-induced neurotoxicity. 6 Our findings indicate that colchicine-induced apoptosis in CGCs is mediated by caspase-3 activation, unlike KA-induced apoptosis. British Journal of Pharmacology (2002).

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Título según WOS: ID WOS:000174384400027 Not found in local WOS DB
Volumen: 135
Número: 5
Editorial: Wiley
Fecha de publicación: 2002
Página de inicio: 1297
Página final: 1307


Notas: ISI