Calcineurin and mitochondrial function in glutamate-induced neuronal cell death
Calcineurin and mitochondrial function in glutamate-induced neuronal cell death
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DOI：
10.1016/0014-5793(96)00959-3
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发表时间：
1996-10-07
期刊：
影响因子：
3.5
通讯作者：
Nicotera, P
中科院分区：
文献类型：
--
作者：
Ankarcrona, M;Dypbukt, JM;Nicotera, P
我们以前曾报道谷氨酸能引起小脑颗粒细胞（CGC）的一系列坏死和凋亡。由于N-甲基-D-天冬氨酸（NMDA）受体通道的特异性阻断剂阻止了这两种类型的细胞死亡，因此我们进一步研究了Ca ~（2+）依赖性过程在谷氨酸毒性启动中的作用。我们研究了线粒体的可能参与和Ca 2 +/钙调蛋白调节的蛋白磷酸酶，钙调磷酸酶，在任何类型的细胞死亡的发展中的作用，环孢菌素A和更有选择性的钙调磷酸酶抑制剂PK-506，阻止了早期坏死和延迟凋亡的发展。环孢菌素A防止了在暴露于谷氨酸和伴随的坏死阶段期间观察到的线粒体膜电位的崩溃。当在谷氨酸去除后立即加入CsA时，它还阻止了在坏死期存活的神经元的延迟凋亡。总之，这些结果表明钙调神经磷酸酶的参与和线粒体脱钙作为谷氨酸诱导的神经元凋亡的早期信号的作用。
We have previously reported that glutamate can trigger a succession of necrosis and apoptosis in cerebellar granule cells (CGC), Since specific blockers of the N-methyl-D-aspartate (NMDA) receptor channel prevented both types of cell death, the role of Ca2+-dependent processes in the initiation of glutamate toxicity,vas further investigated. We examined the possible involvement of mitochondria and the role of the Ca2+/calmodulin-regulated protein phosphatase, calcineurin, in the development of either type of cell death, Cyclosporin A and the more selective calcineurin inhibitor, PK-506, prevented the development of both early necrosis and delayed apoptosis, In addition, cyclosporin A prevented the collapse of mitochondrial membrane potential observed during the exposure to glutamate and the concomitant necrotic phase, When CsA was added immediately after glutamate removal, it also prevented delayed apoptosis of neurons that had survived the necrotic phase, Altogether, these results suggest the involvement of calcineurin and a role for mitochondrial deenergization as early signals in neuronal apoptosis induced by glutamate.