Upregulation of Multidrug Resistance-Associated Protein 1 by Allyl Isothiocyanate in Human Bronchial Epithelial Cell: Involvement of c-Jun N-Terminal Kinase Signaling Pathway.
Multidrug resistance-associated protein 1 (MRP1) plays a protective role in the etiology and progression of chronic obstructive pulmonary disease (COPD) which results from oxidative stress and inflammation of lung injury. The lower functional MRP1 activity is related to COPD development. Our previous study showed that Allyl isothiocyanate (AITC) induced the expression and activity of MRP1 in a dose-dependent manner. However, which signaling pathway contributes to the upregulation of MRP1 by AITC is unclear. In this study, signaling pathway specific inhibitors were used to examine the mechanism of AITC. We found that JNK inhibitor SP600125 treatment decreased MRP1 mRNA expression in 16HBE14o- cells. But the ERK inhibitor U0126 or PI3K/Akt inhibitor LY294002 produced no obvious effect. The AITC-induced increase of MRP1 mRNA expression was abolished by cotreatment of SP600125, while it was not obviously affected by U0126 or LY294002. Furthermore, AITC acivates the JNK signaling pathway in 16HBE14o- cells. Finally, we found that JNK pathway mediated the upregulation of AITC-induced expression and function of MRP1. Taken together, our results indicated that AITC increased the expression and the activity of MRP1 via a JNK-dependent pathway. ERK and PI3K signaling pathway were not involved in the expression of MRP1 mRNA.
Anhui University of Chinese Medicine, Hefei, Anhui 230038, China.
Shujun
S
Wang
Anhui University of Chinese Medicine, Hefei, Anhui 230038, China ; People's Hospital of Feidong County, Hefei, Anhui 230001, China.
Shanshan
S
Wang
Anhui University of Chinese Medicine, Hefei, Anhui 230038, China ; Faculty of Health Sciences, University of Macau, Macau.
Chenyin
C
Wang
Anhui University of Chinese Medicine, Hefei, Anhui 230038, China.
Yajun
Y
Chen
Anhui University of Chinese Medicine, Hefei, Anhui 230038, China.
Jie
J
Li
Anhui University of Chinese Medicine, Hefei, Anhui 230038, China.
Xueqi
X
Wang
Anhui University of Chinese Medicine, Hefei, Anhui 230038, China.
Dianlei
D
Wang
The First Affiliated Hospital to Anhui University of Chinese Medicine, Hefei, Anhui 230031, China.
Zegeng
Z
Li
Anhui University of Chinese Medicine, Hefei, Anhui 230038, China.
Zhaoliang
Z
Peng
Anhui University of Chinese Medicine, Hefei, Anhui 230038, China.
Ling
L
Fan
D001980:Bronchi / Q000166:cytology / Q000473:pathology*; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D017879:Isothiocyanates / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000235:genetics*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation
D017879:Isothiocyanates; D048031:JNK Mitogen-Activated Protein Kinases; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C004471:allyl isothiocyanate; C421109:multidrug resistance-associated protein 1