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

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

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: why1987@ntu.edu.cn.
  • 5 Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, Jiangsu, 226019, China. Electronic address: chengang@ntu.edu.cn.
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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