ATF3 Promotes Arsenic-Induced Apoptosis and Oppositely Regulates DR5 and Bcl-xL Expression in Human Bronchial Epithelial Cells.
ATF3 Promotes Arsenic-Induced Apoptosis and Oppositely Regulates DR5 and Bcl-xL Expression in Human Bronchial Epithelial Cells.
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ATF3 促进砷诱导的细胞凋亡并相反调节人支气管上皮细胞中 DR5 和 Bcl-xL 的表达
DOI：
10.3390/ijms22084223
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发表时间：
2021-04-19
影响因子：
5.6
通讯作者：
Qi N
中科院分区：
文献类型：
--
作者：
Shi Q;Hu B;Yang C;Zhao L;Wu J;Qi N
砷是最常见的环境污染物之一，引起严重的公共卫生问题；然而，它也是公认的急性早幼粒细胞白血病的化疗药物。砷暴露与肺部疾病之间的联系已经确定，但潜在的分子机制还不清楚。在这里，我们研究了呼吸道上皮细胞中砷的毒理作用。砷通过JNK和p38途径快速诱导激活转录因子ATF3的表达。ATF3基因缺失的BEAS-2B细胞对砷诱导的细胞凋亡具有相对的抵抗力，表明ATF3在砷诱导的细胞凋亡中起促进作用。我们进一步证明ATF3通过直接与启动子DR5和Bcl2-xl结合来反向调节死亡受体(DR5)和Bcl2-like 1(Bcl2-xl)的转录。综上所述，我们的研究结果表明，ATF3通过转录调控DR5和Bclxl，在砷诱导的呼吸道上皮细胞凋亡中是一种促凋亡蛋白，突出了ATF3作为砷致肺损伤早期和敏感生物标志物的潜力。
Arsenic is one of the most common environmental pollutants eliciting serious public health issues; however, it is also a well-recognized chemotherapeutic agent for acute promyelocytic leukemia. The association between arsenic exposure and lung diseases has been established, but underlying molecular mechanisms are poorly defined. Here we investigated the toxicology of arsenic in airway epithelium. Arsenic rapidly induced the activating transcription factor ATF3 expression through the JNK and p38 pathways. The ATF3-deficient BEAS-2B cells were relatively resistant to apoptosis upon arsenic exposure, indicating a facilitatory role of ATF3 in arsenic-induced apoptosis. We further showed that ATF3 oppositely regulated the transcription of death receptor (DR5) and Bcl2-like 1 (Bcl-xL) by directly binding to the promoter DR5 and Bcl-xL. Altogether, our findings establish ATF3 as a pro-apoptotic protein in arsenic-induced airway epithelial apoptosis through transcriptionally regulating DR5 and Bcl-xL, highlighting the potential of ATF3 as an early and sensitive biomarker for arsenic-caused lung injury.
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影响因子：
16.6
作者：
Cui, Hongmei;Guo, Mingxiong;Xu, Dong;Ding, Zhi-Chun;Zhou, Gang;Ding, Han-Fei;Zhang, Junran;Tang, Yi;Yan, Chunhong
通讯作者：
Yan, Chunhong
影响因子：
3.6
作者：
Chen QY;Costa M
通讯作者：
Costa M
影响因子：
4.3
作者：
Mahalanobish, Sushweta;Saha, Sukanya;Sil, Parames C.
通讯作者：
Sil, Parames C.
影响因子：
8.3
作者：
Shih, Yu-Hsuan;Argos, Maria;Turyk, Mary E.
通讯作者：
Turyk, Mary E.
影响因子：
7.9
作者：
Sanchez TR;Powers M;Perzanowski M;George CM;Graziano JH;Navas-Acien A
通讯作者：
Navas-Acien A