Allyl isothiocyanate treatment alleviates chronic obstructive pulmonary disease through the Nrf2-Notch1 signaling and upregulation of MRP1.

Abstract

AIMS:

Chronic obstructive pulmonary disease (COPD) is a disease with high morbidity and mortality worldwide, which can cause serious social and economic burdens. Allyl isothiocyanate (AITC) is one of the most common natural isothiocyanates and has been shown to have anti-inflammatory and antioxidant biological activities. The purpose of this study was to investigate whether AITC regulated Multidrug resistance-associated protein 1 (MRP1), reactive oxide species (ROS) and reduced glutathione (GSH) levels via Nrf2 and Notch1 signaling pathways to treat COPD and whether there was an interaction between these two pathways.

MAIN METHODS:

Lung function indexes and histopathological changes in mice were determined by lung function instrument and HE staining, respectively. The protein expression was analyzed using immunohistochemistry and Western blotting. The mRNA expression was measured by RT-PCR in human bronchial epithelial cell line 16HBE. The contents of ROS, GSH and GSSG were detected by kits in 16HBE cells.

KEY FINDINGS:

The protein expression of Notch1, Hes1, MRP1, Nrf2, and HO-1 in lung tissues of WT mice and untransfected cells were significantly down-regulated in COPD, then significantly ameliorated in treatment groups. The protein expression of MRP1, Notch1 and Hes1 in lung tissues of Nrf2-/- mice were markedly reduced. There was a significant reduction in expression of Nrf2, HO-1 and MRP1 in si-Notch1 transfected cells. Pretreatment with AITC markedly improved oxidative stress and GSH-redox disorder in COPD.

SIGNIFICANCE:

Our study demonstrates that there is a potential interaction between Nrf2 and Notch1 signaling pathways during treatment of COPD.

• Authors: Yuanyuan Zhou, Xiaoya Xu, Jie Wu, Lingling Xu, Min Zhang, Zegeng Li, Dianlei Wang
• Journal: Life sciences (Life Sci) Vol. 243 Pg. 117291 (Feb 15 2020) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 31927049 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Hes1 protein, mouse
• Isothiocyanates
• Multidrug Resistance-Associated Proteins
• NF-E2-Related Factor 2
• Nfe2l2 protein, mouse
• Notch1 protein, mouse
• Receptor, Notch1
• Transcription Factor HES-1
• allyl isothiocyanate
• multidrug resistance-associated protein 1

Topics

• Animals
• Isothiocyanates (pharmacology, therapeutic use)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Multidrug Resistance-Associated Proteins (metabolism)
• NF-E2-Related Factor 2 (genetics, metabolism)
• Oxidation-Reduction
• Pulmonary Disease, Chronic Obstructive (drug therapy, metabolism)
• Receptor, Notch1 (metabolism)
• Signal Transduction (drug effects)
• Transcription Factor HES-1 (metabolism)
• Up-Regulation (drug effects)