Inhibition of tyrosine kinases protects against lipopolysaccharide-induced acute lung injury by preventing nuclear export of Nrf2
Inhibition of tyrosine kinases protects against lipopolysaccharide-induced acute lung injury by preventing nuclear export of Nrf2
复制标题
抑制酪氨酸激酶可通过阻止 Nrf2 的核输出来防止脂多糖诱导的急性肺损伤
DOI:
10.1002/jcb.28497
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发表时间:
2019-08-01
影响因子:
4
通讯作者:
Ning, Jiaolin
中科院分区:
文献类型:
--
作者:
Duan, Jiaxiang;Yang, Zhen;Ning, Jiaolin
Acute Lung Injury is a common severe pathological condition that is usually caused by lipopolysaccharide (LPS) infection from bacteria. Enhanced activity of nuclear factor erythroid 2-related factor 2 (Nrf2) could attenuate LPS induced lung injury, However, it still remains unknown whether the enhanced activity of Nrf2 via suppression of Nrf2 nucleus export attenuates the LPS induced lung injury. The aim of this study is to investigate the effects of inhibitors of Fyn on the LPS-induced acute lung injury and to explore its underlying molecular mechanisms. Nrf2 localization in the cells was observed by using confocal microscopy and its transcriptional activation was measured by Electrophoretic Mobility Shift Assay and controlled genes expression levels. The lung injury severity was examined by histopathological scoring and oxidative stress level. In this study, we showed that PP2, LMB, and Nrf2 Y568A abrogated Nrf2 nuclear export and thus enhance the Nrf2 transcriptional activity. PP2 attenuated lung injury and the reduction of cells viability induced by LPS. The current study demonstrated, for the first time, that increase of expression of Nrf2 controlled protective genes via suppression of Nrf2 nucleus export could attenuate lung injury.