Targeting human 8-oxoguanine DNA glycosylase to mitochondria protects cells from 2-methoxyestradiol-induced-mitochondria-dependent apoptosis

被引：7

作者：

Chatterjee, A. ^{[1
]}

Chang, X. ^{[1
]}

Nagpal, J. K. ^{[1
]}

Chang, S. ^{[1
]}

Upadhyay, S. ^{[1
]}

Califano, J. ^{[1
]}

Trink, B. ^{[1
]}

Sidransky, D. ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Head & Neck Canc Res Div, Baltimore, MD 21231 USA

来源：

ONCOGENE | 2008年 / 27卷 / 26期

关键词：

hOGG1; mitochondria; 2-methoxyestradiol; Fas activation;

D O I：

10.1038/onc.2008.3

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

2-Methoxyestradiol (2-ME), an endogenous estrogen metabolite of 17 beta-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 G(2)/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.

引用

页码：3710 / 3720

页数：11

共 78 条

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