Upregulation of Multidrug Resistance-Associated Protein 1 by Allyl Isothiocyanate in Human Bronchial Epithelial Cell: Involvement of c-Jun N-Terminal Kinase Signaling Pathway.
Upregulation of Multidrug Resistance-Associated Protein 1 by Allyl Isothiocyanate in Human Bronchial Epithelial Cell: Involvement of c-Jun N-Terminal Kinase Signaling Pathway.
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DOI：
10.1155/2015/903782
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发表时间：
2015
影响因子：
--
通讯作者：
Fan L
中科院分区：
文献类型：
--
作者：
Wang S;Wang S;Wang C;Chen Y;Li J;Wang X;Wang D;Li Z;Peng Z;Fan L
多药耐药相关蛋白1（MRP 1）在氧化应激和炎症性肺损伤导致的慢性阻塞性肺疾病（COPD）的病因和进展中起保护作用。较低的功能性MRP 1活性与COPD的发展有关。我们前期的研究表明，异硫氰酸烯丙酯（AITC）以剂量依赖的方式诱导MRP 1的表达和活性。然而，哪种信号通路有助于AITC上调MRP 1尚不清楚。在本研究中，信号通路特异性抑制剂被用来研究AITC的机制。我们发现JNK抑制剂SP 600125处理降低16 HBE 140-细胞中MRP 1 mRNA的表达。ERK抑制剂U 0126或PI 3 K/Akt抑制剂LY 294002对细胞凋亡无明显影响。SP 600125可抑制AITC诱导的MRP 1 mRNA表达增加，而U 0126和LY 294002对AITC诱导的MRP 1 mRNA表达无明显影响。此外，AITC激活16 HBE 140-细胞中的JNK信号通路。最后，我们发现JNK通路介导了AITC诱导的MRP 1表达和功能的上调。综上所述，我们的结果表明，AITC通过JNK依赖的途径增加MRP 1的表达和活性。ERK和PI 3 K信号通路不参与MRP 1 mRNA的表达。
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.