Mitochondria play no roles in Mn(II)-induced apoptosis in HeLa cells
Mitochondria play no roles in Mn(II)-induced apoptosis in HeLa cells
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DOI：
10.1073/pnas.181319898
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发表时间：
2001-08-14
影响因子：
11.1
通讯作者：
Chock, PB
中科院分区：
文献类型：
--
作者：
Oubrahim, H;Stadtman, ER;Chock, PB
锰（II）已被证明在生理条件下表现出过氧化氢酶样活性。在测试Mn（II）对HeLa细胞的抗氧化活性的研究过程中，观察到在高浓度（1-2 mM）下Mn（II）也诱导细胞凋亡，如通过细胞形态学的变化、半胱天冬酶-3活化、聚（ADP）核糖的裂解和DNA缩合所判断的。然而，在既定的机制相比，锰（II）诱导的细胞凋亡与线粒体内膜电位的增加，而不是减少，监测的荧光探针四甲基罗丹明乙酯。基于免疫化学分析，Mn（II）诱导的细胞凋亡不会导致细胞色素c释放到胞质溶胶中。这些和其他测量结果表明，Mn（II）的治疗导致线粒体的“膜质量”的增强，对线粒体体积没有影响，并且不影响渗透性转换孔。总之，这些结果支持Mn（II）诱导的细胞凋亡发生的一个迄今未被认识的机制的观点。此外，它表明，Mn（II）的治疗导致增加生产的活性氧（过氧化物）和锰超氧化物歧化酶和过氧化氢酶活性的诱导，但没有影响的铜，锌-超氧化物歧化酶的水平。
Manganese(II) has been shown to exhibit catalase-like activity under physiological conditions. In the course of studies to test the antioxidant activity of Mn(II) on HeLa cells, it was observed at high concentrations; (1-2 mM) that Mn(II) also induced apoptosis, as judged by changes in cell morphology, caspase-3 activation, cleavage of poly(ADP) ribose, and DNA condensation. However, in contrast to established mechanisms,the Mn(II)-induced apoptosis is associated with an increase rather than a decrease in mitochondrial inner-membrane potential, as monitored by the fluorescent probe tetra methyl rhodamine ethyl ester. Based on immunochemical analysis, Mn(II)-induced apoptosis does not lead to the release of cytochrome c into the cytosol. These and other measurements show that treatment with Mn(II) leads to enhancement of the mitochondrial "membrane mass," has no effect on mitochondrial volume, and does not affect the permeability transition pore. Together, these results support the view that Mn(II)-induced apoptosis occurs by a heretofore unrecognized mechanism. In addition, it was demonstrated that Mn(II) treatment leads to an increase in the production of reactive oxygen species (peroxides) and to the induction of the manganese superoxide dismutase and catalase activities but has no effect on the Cu,Zn-superoxide dismutase level.