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首页> 外文期刊>Oncogene >Targeting human 8-oxoguanine DNA glycosylase to mitochondria protects cells from 2-methoxyestradiol-induced-mitochondria-dependent apoptosis
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Targeting human 8-oxoguanine DNA glycosylase to mitochondria protects cells from 2-methoxyestradiol-induced-mitochondria-dependent apoptosis

机译：靶向人类8-氧鸟嘌呤DNA糖基化酶的线粒体保护细胞免受2-甲氧基雌二醇诱导的线粒体依赖性细胞凋亡

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摘要

2-Methoxyestradiol (2-ME), an endogenous estrogen metabolite of 17β-estradiol, is known to induce mitochondria-mediated apoptosis through several mechanisms. We sought to study the effect of mitochondrialy targeted hOGG1 (MTS-hOGG1) on HeLa cells exposed to 2-ME. MTS-hOGG1-expressing cells exposed to 2-ME showed increased cellular survival and had significantly less G2/M cell cycle arrest compared to vector-only-transfected cells. In addition, 2-ME exposure resulted in an increase in mitochondrial membrane potential, increased apoptosis, accompanied by higher activation of caspase-3, -9, cleavage of Bid to tBid and protein poly(ADP-ribose) polymerase (PARP) cleavage in HeLa cells lacking MTS-hOGG1. Fas inhibitors cerulenin or C75 inhibited 2-ME-induced caspase activation, PARP cleavage, apoptosis and reversed mitochondrial membrane hyperpolarization, thereby recapitulating the increased expression of MTS-hOGG1. Hence, MTS-hOGG1 plays an important protective role against 2-ME-mediated mitochondrial damage by blocking apoptosis induced through the Fas pathway.
机译：已知2-甲氧基雌二醇（2-ME）是17β-雌二醇的内源性雌激素代谢产物，它通过多种机制诱导线粒体介导的细胞凋亡。我们试图研究线粒体靶向hOGG1（MTS-hOGG1）对暴露于2-ME的HeLa细胞的影响。与仅转染载体的细胞相比，暴露于2-ME的MTS-hOGG1表达细胞显示出更高的细胞存活率，并且具有明显更少的G2 / M细胞周期停滞。另外，2-ME暴露导致线粒体膜电位增加，细胞凋亡增加，伴随caspase-3，-9的更高活化，Bid裂解为tBid和蛋白聚（ADP-核糖）聚合酶（PARP）裂解。缺乏MTS-hOGG1的HeLa细胞。 Fas抑制剂cerulenin或C75抑制了2-ME诱导的caspase活化，PARP裂解，凋亡和逆转的线粒体膜超极化，从而概括了MTS-hOGG1表达的增加。因此，MTS-hOGG1通过阻止Fas途径诱导的细胞凋亡，对2-ME介导的线粒体损伤起着重要的保护作用。

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