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

Abstract

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.

• Authors: Qiwen Shi, Bei Hu, Chen Yang, Lan Zhao, Jing Wu, Nan Qi
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 8 (Apr 19 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 33921748 (Publication Type: Journal Article)

Chemical References

• Activating Transcription Factor 3
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• TNFRSF10B protein, human
• Arsenic

Topics

• Activating Transcription Factor 3 (genetics, metabolism)
• Apoptosis (drug effects, genetics)
• Arsenic (toxicity)
• Bronchi (cytology)
• Cell Line, Tumor
• Epithelial Cells (drug effects, metabolism)
• Humans
• MAP Kinase Signaling System (drug effects, genetics)
• Promoter Regions, Genetic (drug effects, genetics)
• Receptors, TNF-Related Apoptosis-Inducing Ligand (genetics, metabolism)