pubmed:abstractText |
In the mammalian central nervous system glutamate is the major excitatory neurotransmitter and plays a crucial role in plasticity and toxicity of certain neural cells. We found that glutamate stimulated activation of p38 and stress-activated protein kinase (SAPK, also known as c-Jun N-terminal kinase (JNK)), two subgroup members of the mitogen-activated protein kinase superfamily in matured cerebellar granule cells. The p38 activation was largely mediated by N-methyl-D-aspartate receptors. Furthermore, we have revealed a novel signaling pathway, that is, Ca2+-mediated activation of p38 in glutamate-treated granule cells. The glutamate concentration effective for inducing apoptosis correlated with that for inducing p38 activation. SB203580, a specific inhibitor for p38, inhibited glutamate-induced apoptosis. Thus p38 might be involved in glutamate-induced apoptosis in cerebellar granule cells.
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pubmed:affiliation |
Department of Genetics and Molecular Biology, Institute for Virus Research, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-01, Japan.
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