MitoQ alleviates LPS-mediated acute lung injury through regulating Nrf2/ Drp1 pathway

被引：95

作者：

Hou, Lei ^{[1
]}

Zhang, Jinyuan ^{[1
]}

Liu, Yajing ^{[1
]}

Fang, Hongwei ^{[1
]}

Liao, Lijun ^{[1
]}

Wang, Zhankui ^{[2
]}

Yuan, Jie ^{[3
]}

Wang, Xuebin ^{[1
]}

Sun, Jixiong ^{[1
]}

Tang, Bing ^{[1
]}

Chen, Hongfei ^{[1
]}

Ye, Pengcheng ^{[1
]}

Ding, Zhenmin ^{[1
]}

Lu, Huihong ^{[1
]}

Wang, Yinglin ^{[1
]}

Wang, Xiangrui ^{[1
]}

机构：

[1] Tongji Univ, Shanghai East Hosp, Dept Anesthesiol & Crit Care Med, Sch Med, 150 Jimo Rd, Shanghai 200120, Peoples R China

[2] Shaanxi Univ Chinese Med, Clin Med Coll 1, Dept Orthoped, Xianyang, Shaanxi, Peoples R China

[3] Zunyi Med Univ, Dept Pain, Affiliated Hosp, Zunyi 563000, Guizhou, Peoples R China

来源：

FREE RADICAL BIOLOGY AND MEDICINE | 2021年 / 165卷

基金：

中国国家自然科学基金;

关键词：

LPS; MitoQ; Apoptosis; Mitochondrial fission; Drp1;

D O I：

10.1016/j.freeradbiomed.2021.01.045

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Lipopolysaccharide (LPS) has been known to cause alveolar epithelial cell (AEC) apoptosis and barrier breakdown that characterize acute lung injury (ALI) and acute respiratory distress syndrome. We aimed to investigate whether mitoquinone (MitoQ), a mitochondria-targeted antioxidant, could alleviate LPS-induced AEC damage in ALI and its underlying mechanisms. In vitro studies in AEC A549 cell line, we noted that LPS could induce dynamin-related protein 1 (Drp1)-mediated mitochondrial fission, AEC apoptosis and barrier breakdown, which could be reversed with MitoQ and mitochondrial division inhibitor 1 treatment. Moreover, the protective role of MitoQ was attenuated with Drp1 overexpression. Nuclear factor E2-related factor 2 (Nrf2) downregulation could block the effect of MitoQ by decreasing the expression of Nrf2 target genes in LPS-treated AEC, such as heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1). Nrf2 gene knockdown in LPS-treated A549 cells prevented the protective effect of MitoQ from decreasing Drp1-mediated mitochondrial fission, AEC apoptosis and barrier breakdown. The lung protective effect of MitoQ by regulating the Drp1-mediated mitochondrial fission, AEC apoptosis and barrier breakdown was further confirmed in vivo with LPS-induced ALI mouse model. Additionally, the protective effect of MitoQ was inhibited by Nrf2 inhibitor ML385. We therefore conclude that MitoQ exerts ALI-protective effects by preventing Nrf2/Drp1-mediated mitochondrial fission, AEC apoptosis as well as barrier breakdown.

引用

页码：219 / 228

页数：10

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