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首页> 外文期刊>The Journal of toxicological sciences >Arsenic acid inhibits proliferation of skin fibroblasts, and increases cellular senescence through ROS mediated MST1-FOXO signaling pathway
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Arsenic acid inhibits proliferation of skin fibroblasts, and increases cellular senescence through ROS mediated MST1-FOXO signaling pathway

机译：砷酸通过ROS介导的MST1-FOXO信号通路抑制皮肤成纤维细胞的增殖并增加细胞衰老

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摘要

Arsenic exposure through drinking water is a major public health problem. It causes a number of toxic effects on skin. Arsenic has been reported to inhibit cell proliferation in in vitro conditions. However, reports about the molecular mechanisms are limited. Here, we investigated the mechanism involved in arsenic acid-mediated inhibition of cell proliferation using mouse skin fibroblast cell line. The present study found that 10 ppm arsenic acid inhibited cell proliferation, without any effect on cell death. Arsenic acid induced the generation of reactive oxygen species (ROS), resulting in oxidative stress to DNA. It also activated the mammalian Ste20-like protein kinase 1 (MST1); however the serine/threonine kinase Akt was downregulated. Forkhead box O (FOXO) transcription factors are activated through phosphorylation by MST1 under stress conditions. They are inhibited by phosphorylation by Akt through external and internal stimuli. Activation of FOXOs results in their nuclear localization, followed by an increase in transcriptional activity. Our results showed that arsenic induced the nuclear translocation of FOXO1 and FOXO3a, and altered the cell cycle, with cells accumulating at the G2/M phase. These effects caused cellular senescence. Taken together, our results indicate that arsenic acid inhibited cell proliferation through cellular senescence process regulated by MST1-FOXO signaling pathway.
机译：通过饮用水接触砷是一个主要的公共卫生问题。它对皮肤造成许多毒性作用。据报道砷在体外条件下可抑制细胞增殖。但是，有关分子机制的报道有限。在这里，我们调查了使用小鼠皮肤成纤维细胞细胞系参与砷酸介导的细胞增殖抑制的机制。本研究发现10 ppm的砷酸可抑制细胞增殖，而对细胞死亡没有任何影响。砷酸诱导活性氧（ROS）的产生，从而导致DNA的氧化应激。它还激活了哺乳动物的Ste20样蛋白激酶1（MST1）。然而，丝氨酸/苏氨酸激酶Akt被下调。 MST1在压力条件下通过磷酸化激活了前叉箱O（FOXO）转录因子。它们通过外部和内部刺激被Akt磷酸化抑制。 FOXO的活化导致其核定位，然后转录活性增加。我们的结果表明，砷诱导了FOXO1和FOXO3a的核易位，并改变了细胞周期，细胞在G2 / M期积累。这些作用引起细胞衰老。两者合计，我们的结果表明砷酸通过受MST1-FOXO信号通路调节的细胞衰老过程抑制细胞增殖。

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