AITC induces MRP1 expression by protecting against CS/CSE-mediated DJ-1 protein degradation via activation of the DJ-1/Nrf2 axis
10.4196/kjpp.2020.24.6.481
- Author:
Lingling XU
1
;
Jie WU
;
Nini LI
;
Chengjun JIANG
;
Yan GUO
;
Peng CAO
;
Dianlei WANG
Author Information
1. School of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui 230012, P.R. China
- Publication Type:Original Article
- From:The Korean Journal of Physiology and Pharmacology
2020;24(6):481-492
- CountryRepublic of Korea
- Language:English
-
Abstract:
The present study aimed to examine the effect of allyl isothiocyanate (AITC) on chronic obstructive pulmonary disease and to investigate whether upregulation of multidrug resistance-associated protein 1 (MRP1) associated with the activation of the PARK7 (DJ-1)uclear factor erythroid 2-related factor 2 (Nrf2) axis.Lung function indexes and histopathological changes in mice were assessed by lung function detection and H&E staining. The expression levels of Nrf2, MRP1, heme oxygenase-1 (HO-1), and DJ-1 were determined by immunohistochemistry, Western blotting and reverse transcription-quantitative polymerase chain reaction. Next, the expression of DJ-1 in human bronchial epithelial (16HBE) cells was silenced by siRNA, and the effect of DJ-1 expression level on cigarette smoke extract (CSE)-stimulated protein degradation and AITC-induced protein expression was examined. The expression of DJ-1, Nrf2, HO-1, and MRP1 was significantly decreased in the wild type model group, while the expression of each protein was significantly increased after administration of AITC. Silencing the expression of DJ-1 in 16HBE cells accelerated CSE-induced protein degradation, and significantly attenuated the AITC-induced mRNA and protein expression of Nrf2 and MRP1. The present study describes a novel mechanism by which AITC induces MRP1 expression by protecting against CS/CSEmediated DJ-1 protein degradation via activation of the DJ-1/Nrf2 axis.
