Neuroprotective effect of KB-R7943 against glutamate excitotoxicity is related to mild mitochondrial depolarization.
Neuroprotective effect of KB-R7943 against glutamate excitotoxicity is related to mild mitochondrial depolarization.
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KB-R7943 针对谷氨酸兴奋毒性的神经保护作用与轻度线粒体去极化有关。
DOI：
10.1007/s11064-009-0058-x
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发表时间：
2010
影响因子：
4.4
通讯作者：
Brustovetsky,N
中科院分区：
文献类型：
--
作者：
Storozhevykh,TP;Senilova,YaE;Brustovetsky,T;Pinelis,VG;Brustovetsky,N
KB-R7943是一种Na+/Ca 2+交换抑制剂，对谷氨酸兴奋性毒性具有神经保护作用。考虑到神经元长时间暴露于谷氨酸可诱导迟发性钙失调（DCD）和线粒体膜电位（Δ mit）的不可逆降低，我们研究了KB-R7943对谷氨酸和红藻氨酸诱导的大鼠小脑颗粒神经元[Ca 2 +] i和Δ mit变化的影响。15 μmol/l KB-R7943可显著延迟红藻氨酸诱导的DCD发作，但对谷氨酸无明显影响。尽管[Ca ~（2+）] i超负荷，但KB-R7943显著改善谷氨酸和红藻氨酸洗脱后[Ca ~（2+）] i的恢复和Δ CaM的恢复，并增加谷氨酸暴露后的细胞活力。在静息神经元中，KB-R7943诱导Δ Δ的统计学显著降低。KB-R7943还使分离的脑线粒体去极化，并轻微抑制线粒体Ca 2+摄取。提示KB-R7943的神经保护作用可能与线粒体轻度去极化和细胞器内Ca ~（2+）积累减少有关。
KB-R7943, an inhibitor of a reversed Na+/Ca2+exchanger, exhibits neuroprotection against glutamate excitotoxicity. Taking into consideration that prolonged exposure of neurons to glutamate induces delayed calcium deregulation (DCD) and irreversible decrease of mitochondrial membrane potential (Δψmit), we examined the effect of KB-R7943 on glutamate and kainate-induced [Ca2+]iand on Δψmitchanges in rat cultured cerebellar granule neurons. 15 μmol/l KB-R7943 significantly delayed the onset of DCD in response to kainate but not in response to glutamate. In spite of [Ca2+]ioverload, KB-R7943 considerably improved the [Ca2+]irecovery and restoration of Δψmitafter glutamate and kainate washout and increased cell viability after glutamate exposure. In resting neurons, KB-R7943 induced a statistically significant decrease in Δψmit. KB-R7943 also depolarized isolated brain mitochondria and slightly inhibited mitochondrial Ca2+uptake. These findings suggest that mild mitochondrial depolarization and diminution of Ca2+accumulation in the organelles might contribute to neuroprotective effect of KB-R7943.