Arsenite-induced downregulation of occludin in mouse lungs and BEAS-2B cells via the ROS/ERK/ELK1/MLCK and ROS/p38 MAPK signaling pathways

  • Toxicol Lett. 2020 Oct 10;332:146-154. doi: 10.1016/j.toxlet.2020.07.010.
Yingqi Liu  1 ,  Jing Tang  1 ,  Jiaming Yuan  1 ,  Chenjuan Yao  2 ,  Kazuo Hosoi  3 ,  Yu Han  1 ,  Shali Yu  1 ,  Haiyan Wei  4 ,  Gang Chen  5
Affiliations
  • 1. Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, Jiangsu, 226019, China.
  • 2. Department of Molecular Oral Physiology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima-Shi, Tokushima, 770-8504, Japan.
  • 3. Department of Molecular Oral Physiology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima-Shi, Tokushima, 770-8504, Japan; Kosei Pharmaceutical Co. Ltd., Osaka-shi, Osaka, 540-0039, Japan.
  • 4. Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, Jiangsu, 226019, China. Electronic address: [email protected].
  • 5. Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, Jiangsu, 226019, China. Electronic address: [email protected].
PMID: 32683294 DOI: 10.1016/j.toxlet.2020.07.010
Abstract

Occludin is an important tight junction (TJ) protein in pulmonary epithelial cells. In this study, we identified changes in occludin in arsenic-induced lung injury in vivo and in vitro. Upon intratracheal instillation with arsenic trioxide (As2O3) at a daily dose of 30 μg/kg for 1 week, levels of occludin mRNA and protein expression decreased significantly in mouse lung tissue. Levels of occludin mRNA and protein expression in BEAS-2B cells were reduced upon exposure to As2O3 in a concentration- and time-dependent manner. In addition, exposure to As2O3 significantly increased expression of p-p38, p-ERK1/2, p-ELK1, and MLCK in mouse lung tissue and BEAS-2B cells. Treatment with As2O3 induced oxidative stress in mouse lung tissue and BEAS-2B cells. In BEAS-2B cells, exposure to As2O3 reduced transepithelial resistance, which was partially restored with N-acetyl-cysteine (NAC) treatment. Reduced expression of occludin mRNA and protein induced by As2O3 was entirely restored with NAC and resveratrol. However, SB203580, PD98059, and ML-7 partially blocked As2O3-induced occludin reduction in BEAS-2B cells. These results indicate that As2O3 inhibits occludin expression in vivo and in vitro at least partially via the ROS/ERK/ELK1/MLCK and ROS/p38 MAPK signaling pathways.

Keywords
Arsenic trioxide; ELK1; MAPK signaling pathway; MLCK; Occludin; ROS.
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