Cyclosporin A delays mitochondrial depolarization induced by N-methyl-D-aspartate in cortical neurons: evidence of the mitochondrial permeability transition.
Cyclosporin A delays mitochondrial depolarization induced by N-methyl-D-aspartate in cortical neurons: evidence of the mitochondrial permeability transition.
复制标题
环孢素 A 延迟皮质神经元中 N-甲基-D-天冬氨酸诱导的线粒体去极化：线粒体通透性转变的证据。
DOI：
10.1016/0306-4522(96)00378-8
复制
发表时间：
1996
期刊：
影响因子：
3.3
通讯作者：
Selman,WR
中科院分区：
文献类型：
--
作者：
Nieminen,AL;Petrie,TG;Lemasters,JJ;Selman,WR
n -甲基- d -天冬氨酸引起细胞内Ca2+快速增加，导致线粒体膜电位崩溃，最终导致皮质神经元细胞死亡。本研究的目的是利用激光扫描共聚焦显微镜研究线粒体去极化的机制。为了监测线粒体膜电位，用四甲基罗丹明甲酯标记神经元线粒体，四甲基罗丹明甲酯是一种在极化线粒体中积累的阳离子荧光团。在聚d -赖氨酸包被盖层上培养的神经元中，n -甲基- d -天冬氨酸在30分钟内导致88%的细胞线粒体去极化。环孢素A，线粒体通透性转变的抑制剂，以剂量依赖的方式延迟去极化（0.2-1微米）。在星形胶质细胞饲养层培养的神经元中，n -甲基- d -天冬氨酸也引起线粒体去极化。环孢素A再次延迟线粒体去极化，尽管需要更高的浓度。这些数据首次表明n -甲基- d -天冬氨酸诱导的线粒体去极化可能是由于诱导线粒体通透性转变。
N-Methyl-D-aspartate causes a rapid increase in intracellular Ca2+ leading to collapse of the mitochondrial membrane potential and eventually cell death in cortical neurons. The aim of this study was to investigate the mechanism responsible for mitochondrial depolarization using laser scanning confocal microscopy of single cultured rate cortical neurons. To monitor mitochondrial membrane potential, neuronal mitochondria were labeled with tetramethylrhodamine methyl ester, a cationic fluorophore that accumulates in polarized mitochondria. In neurons cultured on poly-D-lysine-coated coverslips, N-methyl-D-aspartate caused mitochondrial depolarization in 88% of cells in 30 min. Cyclosporin A, an inhibitor of the mitochondrial permeability transition, delayed depolarization in a dose-dependent manner (0.2-1 microM). In neurons cultured on an astrocyte feeder layer, N-methyl-D-aspartate also caused mitochondrial depolarization. Cyclosporin A again delayed mitochondrial depolarization, although higher concentrations were needed. These data show for the first time that mitochondrial depolarization induced by N-methyl-D-aspartate may be due to the induction of the mitochondrial permeability transition.