Arsenic trioxide induces expression of BCL-2 expression via NF-κB and p38 MAPK signaling pathways in BEAS-2B cells during apoptosis

• Published in: Ecotoxicology and environmental safety Vol. 222; p. 112531
• Main Authors: Tang, Jing, Yao, Chenjuan, Liu, Yingqi, Yuan, Jiaming, Wu, Li, Hosoi, Kazuo, Yu, Shali, Huang, Chunyan, Wei, Haiyan, Chen, Gang
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-10-2021; Elsevier
• Subjects: Apoptosis; Arsenic trioxide; BCL-2; NF-κB; p38 MAPK; Phosphorylation; BCL-2; NF-κB; Arsenic trioxide; Phosphorylation; p38 MAPK; Apoptosis
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2021.112531

Inorganic arsenic compounds are environmental toxicants that are widely distributed in air, water, and food. B-cell lymphoma 2 (BCL-2) is an oncogene having anti-apoptotic function. In this study, we clarify that BCL-2, as a pro-apoptotic factor, participates in As2O3-induced apoptosis in BEAS-2B cells. Specifically, As2O3 stimulated the expression of BCL-2 mRNA and protein in a dose-dependent manner which was highly accumulated in the nucleus of BEAS-2B cell together with chromatin condensation and DNA fragmentation during apoptosis. Mechanistically, the process described above is mediated through the NF-κB and p38 MAPK signaling pathways, which can be abated by corresponding inhibitors, such as BAY11–7082 and SB203580, respectively. Additionally, BAY11–7082, actinomycin D, and cycloheximide have inhibitory effects on As2O3-induced expression of BCL-2 mRNA and protein, and restore the cell viability of BEAS-2B cells. Suppression of BCL-2 protein activation by ABT-199 also restored viability of BEAS-2B cell in As2O3-induced apoptosis. Furthermore, As2O3 increased the level of BCL-2 phosphorylation. These results suggest that in BEAS-2B cells, As2O3-induced apoptosis is mainly dominated by BCL-2 upregulation, nuclear localization and phosphorylation. The study presented here provides a novel insight into the molecular mechanism of BCL-2-induced apoptosis.
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•As2O3 increased BCL-2 level in a dose- and time-dependent manner in BEAS-2B cells.•The NF-κB and p38 MAPK pathways were involved in As2O3-induced BCL-2 expression.•As2O3 induced apoptosis by accumulation and phosphorylation of BCL-2 in nucleus.