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首页> 外文期刊>Journal of Neurochemistry: Offical Journal of the International Society for Neurochemistry >Cytochrome c release precedes mitochondrial membrane potential loss in cerebellar granule neuron apoptosis: lack of mitochondrial swelling.
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Cytochrome c release precedes mitochondrial membrane potential loss in cerebellar granule neuron apoptosis: lack of mitochondrial swelling.

机译:在小脑颗粒神经元凋亡中,细胞色素C的释放先于线粒体膜电位的丧失:线粒体肿胀的缺乏。

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摘要

It has been suggested that release of cytochrome c (Cyt c) from mitochondria during apoptotic death is through opening of the mitochondrial permeability transition pore followed by swelling-induced rupture of the mitochondrial outer membrane. However, this remains controversial and may vary with cell type and model system. We determined that in mouse cerebellar granule neurons, Cyt c redistribution preceded the loss of mitochondrial membrane potential during the apoptotic process, suggesting that the pore did not open prior to release. Furthermore, when mitochondria were morphologically assessed by electron microscopy, they were not obviously swollen during the period of Cyt c release. This indicates that the pore mechanism of action, if any, is not through mitochondrial outer membrane rupture. While bongkrekic acid, an inhibitor of pore opening, modestly delayed apoptotic death, it also caused a significant (p < 0.05) suppression of protein synthesis. An equivalent suppression of protein synthesis by cycloheximide had a similar delaying effect, suggesting that bongkrekic acid was acting non-specifically. These findings suggest that mitochondrial permeability transition pore is not involved in Cyt c release from mitochondria during the apoptotic death of cerebellar granule neurons.
机译:已经提出在凋亡死亡期间从线粒体释放细胞色素c(Cyt c)是通过打开线粒体通透性过渡孔,然后溶胀诱导的线粒体外膜破裂。但是,这仍然存在争议,并且可能随单元格类型和模型系统而异。我们确定在小鼠小脑颗粒神经元中,细胞凋亡过程中Cyt c的重新分布先于线粒体膜电位的丧失,这表明孔在释放前并未打开。此外,当通过电子显微镜对线粒体进行形态学评估时,在Cyt c释放期间它们没有明显肿胀。这表明孔的作用机理(如果有的话)不是通过线粒体外膜破裂。奉开酸(一种开孔抑制剂)适度延迟了细胞凋亡的死亡,但它也引起了蛋白质合成的显着(p <0.05)抑制。环己酰亚胺对蛋白质合成的等效抑制作用具有类似的延迟作用,表明邦克里奇酸的作用是非特异性的。这些发现表明,在小脑颗粒神经元凋亡死亡期间,线粒体通透性过渡孔不参与线粒体Cyt c的释放。

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