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Neuroscience. 2003;117(4):899-907.

Ammonia prevents glutamate-induced but not low K(+)-induced apoptosis in cerebellar neurons in culture.

Author information

1
Laboratorio de Neurobiología, Instituto de Investigaciones Citológicas de la FVIB, Amadeo de Saboya, 4 46010, Valencia, Spain.

Abstract

Cultured rat cerebellar granule neurons are widely used as a model system for studying neuronal apoptosis. Either low K(+) (5 mM) or low concentrations of glutamate (1-10 microM) induce apoptosis in cerebellar neurons in culture. However, the molecular mechanism(s) involved remain unclear. We show that long-term treatment with ammonia prevents glutamate-induced but not low K(+)-induced apoptosis in cerebellar neurons, as assessed by measuring DNA fragmentation and activation of caspase 3. Ammonia prevented glutamate-induced increase of intracellular calcium, depolarization of the inner mitochondrial membrane, release of cytochrome c to the cytosol, activation of caspase 3 and fragmentation of DNA. However, ammonia did not prevent low K(+)-induced activation of caspase 3 and fragmentation of DNA. These results indicate that the initial steps involved in the induction of apoptosis by low K(+) or by glutamate are different and that ammonia prevents glutamate-induced apoptosis by reducing glutamate-induced rise of intracellular Ca(2+), thus avoiding the activation of subsequent events of the apoptotic process.

PMID:
12654341
DOI:
10.1016/s0306-4522(02)00957-0
[Indexed for MEDLINE]

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