Low dose arsenite confers resistance to UV induced apoptosis via p53-MDM2 pathway in ketatinocytes.
Low dose arsenite confers resistance to UV induced apoptosis via p53-MDM2 pathway in ketatinocytes.
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低剂量亚砷酸盐通过 p53-MDM2 途径赋予酮形成细胞对紫外线诱导的细胞凋亡的抵抗力
DOI：
10.1038/oncsis.2017.67
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发表时间：
2017-08-07
期刊：
影响因子：
6.2
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Zhou Y;Zeng W;Qi M;Duan Y;Su J;Zhao S;Zhong W;Gao M;Li F;He Y;Hu X;Xu X;Chen X;Peng C;Zhang J
慢性亚砷酸盐和紫外线（UV）暴露与皮肤肿瘤有关。为了研究低浓度亚砷酸盐和UV诱导的皮肤致癌作用的细节，使用hTERT永生化的人角质形成细胞作为暴露于低浓度亚砷酸钠和UV的细胞模型。流式细胞术和Hoechst染色检测NaAsO2对UV诱导的细胞凋亡的影响。我们发现，紫外线照射诱导的细胞凋亡显着减弱暴露后，低剂量砷，敲低p53可以阻断紫外线诱导的细胞凋亡，表明这种现象依赖于p53。有趣的是，小鼠双微体2（MDM2）的表达，包括其蛋白质和转录水平，在暴露于低剂量亚砷酸盐后显著升高。此外，低剂量的亚砷酸盐处理显着降低MDM2基因启动子活性，表明这种影响已通过转录介导。另外，PD98059可逆转低剂量砷诱导的MDM2表达，抑制ERK 2表达可显著阻断MDM2的表达，并自动增加p53的表达。为了验证p53在低剂量砷暴露中的作用，通过免疫组织化学方法检测了慢性砷暴露6个月的Sprague−道利大鼠模型和砷角化病患者皮肤中p53的表达，结果显示，这些样品中p53的表达降低。综上所述，我们的研究结果表明，低剂量亚砷酸盐诱导角质形成细胞通过MDM 2介导的p53细胞凋亡的阻力。
Chronic arsenite and ultraviolet (UV) exposure are associated with skin tumor. To investigate the details by low concentrations of arsenite and UV induced carcinogenesis in skin, hTERT-immortalized human keratinocytes were used as a cellular model with exposure to low concentrations of sodium arsenite and UV. The effect of NaAsO 2 on UV treatment-induced apoptosis was measured by flow cytometry and Hoechst staining. We found that the cell apoptosis induced by UV exposure was significantly attenuated after exposure to low-dose arsenite, and knockdown of p53 could block UV-induced apoptosis indicating that this phenomenon depended on p53. Interestingly, the expression of murine double minute 2 (MDM2), including its protein and transcriptional levels, was remarkably high after exposure to low-dose arsenite. Moreover, low-dose arsenite treatment dramatically decreased the MDM2 gene promoter activity, suggesting that this effect has been mediated through transcription. In addition, treatment of PD98059 reversed low-dose arsenite-induced MDM2 expression, and the inhibition of ERK2 expression could significantly block MDM2 expression as a consequence, and p53 expression automatically was increased. To validate the role of p53 in exposure to low-dose arsenite, the expression of p53 was examined by immunohistochemistry in the skin of Sprague− Dawley rats model by chronic arsenite exposure for 6 months and in patients with arsenic keratosis, and the results showed that the expression of p53 was decreased in those samples. Taken together, our results demonstrated that low-dose arsenite-induced resistance to apoptosis through p53 mediated by MDM2 in keratinocytes.
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影响因子：
64.8
作者：
Bartkova, J;Horejsi, Z;Bartek, J
通讯作者：
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影响因子：
10.4
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10.1006/bbrc.1999.1395
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影响因子：
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作者：
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