Involvement of water channel Aquaporin 5 in H2S-induced pulmonary edema

Environ Toxicol Pharmacol. 2017 Jan:49:202-211. doi: 10.1016/j.etap.2016.12.013. Epub 2016 Dec 30.

Abstract

Acute exposure to hydrogen sulfide (H2S) poses a significant threat to life, and the lung is one of the primary target organs of H2S. However, the mechanisms involved in H2S-induced acute pulmonary edema are poorly understood. This study aims to investigate the effects of H2S on the expression of water channel aquaporin 5 (AQP5) and to elucidate the signaling pathways involved in AQP5 regulation. In an in vivo study, C57BL6 mice were exposed to sub-lethal concentrations of inhaled H2S, and histological injury of the lungs and ultrastructure injury of the epithelial cells were evaluated. With real-time PCR and western blot assays, we found that H2S exposure contributed to a significant decrease in AQP5 expression both in murine lung tissue and the A549 cell line, and the ERK1/2 and p38 MAPK signaling pathways were demonstrated to be implicated in AQP5 regulation. Therefore, adjusting AQP5 protein levels could be considered a therapeutic strategy for the treatment of APE induced by H2S and other hazardous gases.

Keywords: Aquaporin 5; ERK1/2; Hydrogen sulfide; JNK; Pulmonary edema; p38 MAPK.

MeSH terms

  • A549 Cells
  • Animals
  • Aquaporin 5 / genetics
  • Aquaporin 5 / metabolism*
  • Epithelial Cells / drug effects
  • Epithelial Cells / pathology
  • Epithelial Cells / ultrastructure
  • Humans
  • Hydrogen Sulfide / toxicity*
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Lung / ultrastructure
  • Male
  • Mice, Inbred C57BL
  • Microscopy, Electron, Transmission
  • Mitogen-Activated Protein Kinases / metabolism
  • Pulmonary Edema / chemically induced*
  • Pulmonary Edema / metabolism*
  • Pulmonary Edema / pathology
  • RNA, Messenger / metabolism

Substances

  • Aquaporin 5
  • RNA, Messenger
  • Mitogen-Activated Protein Kinases
  • Hydrogen Sulfide