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

Ecotoxicol Environ Saf. 2021 Oct 1:222:112531. doi: 10.1016/j.ecoenv.2021.112531. Epub 2021 Jul 21.

Abstract

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.

Keywords: Apoptosis; Arsenic trioxide; BCL-2; NF-κB; Phosphorylation; p38 MAPK.

MeSH terms

  • Apoptosis*
  • Arsenic Trioxide / toxicity
  • Arsenicals*
  • NF-kappa B / genetics
  • Oxides / toxicity
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • p38 Mitogen-Activated Protein Kinases / genetics

Substances

  • Arsenicals
  • NF-kappa B
  • Oxides
  • Proto-Oncogene Proteins c-bcl-2
  • p38 Mitogen-Activated Protein Kinases
  • Arsenic Trioxide