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DOI QR Code

AITC induces MRP1 expression by protecting against CS/CSE-mediated DJ-1 protein degradation via activation of the DJ-1/Nrf2 axis

  • Xu, Lingling (School of Pharmacy, Anhui University of Chinese Medicine) ;
  • Wu, Jie (School of Pharmacy, Anhui University of Chinese Medicine) ;
  • Li, Nini (School of Pharmacy, Anhui University of Chinese Medicine) ;
  • Jiang, Chengjun (School of Pharmacy, Anhui University of Chinese Medicine) ;
  • Guo, Yan (School of Pharmacy, Anhui University of Chinese Medicine) ;
  • Cao, Peng (Laboratory of Cellular and Molecular Biology, Jiangsu Academy of Chinese Medicine) ;
  • Wang, Dianlei (School of Pharmacy, Anhui University of Chinese Medicine)
  • 투고 : 2020.06.02
  • 심사 : 2020.07.20
  • 발행 : 2020.11.01

초록

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)/nuclear 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/CSE-mediated DJ-1 protein degradation via activation of the DJ-1/Nrf2 axis.

키워드

참고문헌

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