Reactive Oxygen Species Play a Central Role in Hexavalent Chromium-Induced Apoptosis in Hep3B Cells without the Functional Roles of p53 and Caspase-3
Reactive Oxygen Species Play a Central Role in Hexavalent Chromium-Induced Apoptosis in Hep3B Cells without the Functional Roles of p53 and Caspase-3
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DOI：
10.1159/000354436
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发表时间：
2013-07
影响因子：
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通讯作者：
M. Zeng;F. Xiao;X. Zhong;Feng Jin;L. Guan;An Wang;Xinmin Liu;Cai-gao Zhong
中科院分区：
文献类型：
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作者：
M. Zeng;F. Xiao;X. Zhong;Feng Jin;L. Guan;An Wang;Xinmin Liu;Cai-gao Zhong
背景/目的：六价铬[Cr(VI)]及其化合物具有遗传毒性和致突变性，广泛应用于冶金、纺织、电镀等行业。尽管大量文献支持p53和caspase-3在Cr（VI）诱导的细胞毒性中发挥关键作用，但很明显，Cr（VI）诱导细胞凋亡既可以不激活caspase，也可以不依赖于p53。方法：本研究通过Z-VAD-fmk抑制p53缺失的Hep3B细胞的caspase-3，探讨在p53和caspase同时被阻断的情况下，Cr（VI）诱导凋亡的作用及其机制。结果：我们发现，在没有p53和caspase-3功能作用的情况下，Cr（VI）仍能诱导Hep3B细胞的DNA损伤、线粒体损伤、氧化应激和凋亡，并且机制研究表明，这是ros依赖的，NAC共处理对Cr（VI）诱导的细胞凋亡具有保护作用。结论：我们的研究揭示了p53和caspase-3功能丧失后Cr（VI）诱导细胞毒性的机制，并阐明了在Cr（VI）职业暴露人群中使用抗氧化剂进行一级和二级预防的重要性。
Background/Aims: Hexavalent chromium [Cr(VI)] and its compounds, which have the extensive application in diverse industries including metallurgy, textile and electroplating, are known to be genotoxic and mutagenic to humans. Although it is supported by a large body of literatures that p53 and caspase-3 played key roles in Cr(VI)-induced cytotoxicity, it is clear that Cr(VI) could induce apoptosis either without activating caspase, or in a p53-independent manner. Methods: In the present study, by using Z-VAD-fmk to inhibit caspase-3 in p53-deficient Hep3B cells, we explored the effect of Cr(VI) on apoptosis induction and the related mechanisms when the functions of p53 and caspase were simultaneously blocked. Results: We found that Cr(VI) still induced DNA damage, mitochondrial injury, oxidative stress and apoptosis in Hep3B cells without the functional roles of p53 and caspase-3, and the mechanism study revealed that this was in a ROS-dependent manner since NAC co-treatment showed the protective effect against Cr(VI)-induced apoptosis. Conclusion: Our research has disclosed the mechanism involved in Cr(VI)-induced cytotoxicity following the loss of p53 and caspase-3 functions and shed light on the importance of using antioxidants for primary and secondary prevention in Cr(VI) occupational exposure populations.