ATF3 Promotes Arsenic-Induced Apoptosis and Oppositely Regulates DR5 and Bcl-xL Expression in Human Bronchial Epithelial Cells

International Journal of Molecular Sciences

Jing Wu¹  Qiwen Shi¹  Chen Yang¹  Bei Hu¹  Lan Zhao¹  Nan Qi¹ 

[1] Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Institute of Engineering Biology and Health, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, China;

关键词: arsenic;    ATF3;    Bcl-xL;    DR5;    apoptosis;   

DOI  :  10.3390/ijms22084223

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown