MEHP-induced oxidative DNA damage and apoptosis in HepG2 cells correlates with p53-mediated mitochondria-dependent signaling pathway.
MEHP-induced oxidative DNA damage and apoptosis in HepG2 cells correlates with p53-mediated mitochondria-dependent signaling pathway.
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DOI：
10.1016/j.fct.2012.04.023
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发表时间：
2012-07
期刊：
影响因子：
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通讯作者：
Guangtao Yang;Xuebin Zhou;Jing Wang;Wenjuan Zhang;Hongyan Zheng;Wenhong Lu;Jing Yuan
中科院分区：
文献类型：
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作者：
Guangtao Yang;Xuebin Zhou;Jing Wang;Wenjuan Zhang;Hongyan Zheng;Wenhong Lu;Jing Yuan
本研究观察了MEHP对人肝癌HepG 2细胞的作用。结果表明，MEHP处理组（25.00μM）在处理后24 h和100.00μM处理组在处理后36 h均能诱导DNA氧化损伤（p<0.05或p<0.01）。在处理后36 h，较高浓度的MEHP（约25.00μM）导致ATP水平降低，细胞质中细胞色素c和Smac/DIABLO蛋白水平以及凋亡细胞百分比增加。caspase-9和caspase-3的激活以及所选的凋亡相关蛋白p53、p54 A、NOXA、Bax和Bcl-2的表达也被诱导。此外，维生素C，活性氧清除剂，衰减MEHP诱导的细胞凋亡。这些结果表明，MEHP诱导的DNA氧化损伤和凋亡的HepG 2细胞，和p53及其下游蛋白参与线粒体和caspase介导的凋亡MEHP诱导。
In the present study, the effects of MEHP on human hepatocellular liver carcinoma HepG2 cells were investigated. The results showed that MEHP-induced oxidative DNA damage in the treatment groups (⩾25.00μM) at 24h after treatment and in the 100.00μM treatment group at 36h after treatment (p<0.05 or p<0.01). At 36h after treatment, MEHP at higher concentrations (⩾25.00μM) resulted in a decrease in ATP level, and an increase in the protein levels of cytochrome c and Smac/DIABLO in the cytosol as well as the percentage of apoptotic cells. The activation of caspase-9 and -3 and the expression of the selected apoptosis-related proteins, p53, PUMA, NOXA, Bax and Bcl-2 were also induced. Furthermore, vitamin C, a scavenger of reactive oxygen species, attenuated MEHP-induced apoptosis. These findings indicated that MEHP induced oxidative DNA damage and apoptosis in HepG2 cells, and p53 and its downstream proteins were involved in mitochondria- and caspase-mediated apoptosis induced by MEHP.