Over-expression of Bcl-2 does not protect cells from hypericin photo-induced mitochondrial membrane depolarization, but delays subsequent events in the apoptotic pathway
Over-expression of Bcl-2 does not protect cells from hypericin photo-induced mitochondrial membrane depolarization, but delays subsequent events in the apoptotic pathway
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DOI：
10.1016/s0014-5793(99)01538-0
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发表时间：
1999-12-03
期刊：
影响因子：
3.5
通讯作者：
Sureau, F
中科院分区：
文献类型：
--
作者：
Chaloupka, R;Petit, PX;Sureau, F
金丝桃素(HY)是一种强大的光诱导剂，通过caspase-3激活、细胞收缩、磷脂酰丝氨酸(PS)暴露和亚倍体DNA的出现来衡量，这些过程之前是快速的不依赖于Bcl-2的线粒体跨膜去极化和细胞质pH下降，预先与线粒体通透性转换孔抑制剂如环孢素A或bongkrekic酸孵育细胞，不能保护细胞免受线粒体膜电位(Delta psi(M))下降的影响。然而，通过共聚焦荧光成像对包裹在线粒体中的钙黄绿素的监测提供了HY光诱导线粒体通透性的明确证据，这应该被认为是由于脂质过氧化导致线粒体膜完整性的非特异性改变的结果，然而，抗凋亡蛋白Bcl-2的合成似乎推迟了随后PS暴露的时间进程，并减少了caspase-3的激活和亚倍体细胞的比例，我们将这种部分保护作用解释为Bcl-2与先前在Delta psi(M)上从线粒体释放的胞浆细胞色素c直接相互作用的结果。减少和/或抑制caspase-3对线粒体通透性转换孔和/或线粒体膜成分的有害逆转作用，(C)1999年欧洲生化学会联合会。
Hypericin (HY) is a powerful photo-inducer of apoptosis in Jurkat cells as measured by caspase-3 activation, cell shrinkage, phosphatidylserine (PS) exposure and the appearance of hypoploid DNA, These processes are preceded by rapid Bcl-2-independent mitochondrial transmembrane depolarization and a drop in cytoplasmic pH, Pre-incubation of cells with inhibitors of the mitochondrial permeability transition pore, such as cyclosporin A or bongkrekic acid, does not protect cells from mitochondrial membrane potential (Delta psi(m)) decrease. However, monitoring of mitochondrial entrapped calcein by confocal fluorescence imaging gives clear evidence of HY photo-induced mitochondrial permeability, This should be considered as the result of a non-specific alteration of mitochondrial membrane integrity brought about by lipid peroxidation, Nevertheless, synthesis of the anti-apoptotic protein Bcl-2 appears to delay the subsequent time course of PS exposure and to reduce caspase-3 activation and the fraction of cells which become hypoploid, We interpret this partially protective effect as the consequence of a direct interaction of Bcl-2 with cytosolic cytochrome c previously released from mitochondria upon Delta psi(m), decrease and/or of Bcl-2 inhibition of the deleterious retro-effect of caspase-3 on the mitochondrial permeability transition pore and/or the mitochondrial membrane components, (C) 1999 Federation of European Biochemical Societies.