Activation and Involvement of p38 Mitogen-activated Protein Kinase in Glutamate-induced Apoptosis in Rat Cerebellar Granule Cells

• DOI: 10.1074/jbc.272.30.18518
• Publication Date: 2002-07-26T14:57:46Z
• Authors: Hiroshi Kawasaki; Takaya Morooka; Shun Shimohama; Jun Kimura; Tomoo Hirano; Yukiko Gotoh; Eisuke Nishida
• Keywords: 0303 health sciences; N-Methylaspartate; Ionophores; JNK Mitogen-Activated Protein Kinases; Glutamic Acid; Apoptosis; p38 Mitogen-Activated Protein Kinases; Rats; 3. Good health; Enzyme Activation; 03 medical and health sciences; Cerebellum; Calcium-Calmodulin-Dependent Protein Kinases; Excitatory Amino Acid Agonists; Animals; Humans; Calcium; Calcium Channels; Mitogen-Activated Protein Kinases; Calcimycin; Cells, Cultured; Signal Transduction

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.