Kawasaki H, Morooka T, Shimohama S, Kimura J, Hirano T, Gotoh Y, Nishida E
Department of Genetics and Molecular Biology, Institute for Virus Research, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-01, Japan.
J Biol Chem. 1997 Jul 25;272(30):18518-21. doi: 10.1074/jbc.272.30.18518.
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.
在哺乳动物中枢神经系统中，谷氨酸是主要的兴奋性神经递质，在某些神经细胞的可塑性和毒性方面发挥着关键作用。我们发现，谷氨酸能刺激成熟小脑颗粒细胞中丝裂原活化蛋白激酶超家族的两个亚组成员p38和应激激活蛋白激酶（SAPK，也称为c-Jun氨基末端激酶（JNK））的活化。p38的活化主要由N-甲基-D-天冬氨酸受体介导。此外，我们揭示了一条新的信号通路，即在谷氨酸处理的颗粒细胞中Ca2+介导的p38活化。诱导凋亡的有效谷氨酸浓度与诱导p38活化的浓度相关。p38的特异性抑制剂SB203580可抑制谷氨酸诱导的凋亡。因此，p38可能参与了小脑颗粒细胞中谷氨酸诱导的凋亡。
