Polydatin mediates Parkin-dependent mitophagy and protects against mitochondria-dependent apoptosis in acute respiratory distress syndrome

被引:51
作者
Li, Tao [1 ,2 ]
Liu, Youtan [3 ]
Xu, Wei [1 ]
Dai, Xingui [2 ]
Liu, Ruimeng [3 ]
Gao, Youguang [4 ]
Chen, Zhongqing [1 ]
Li, Yunfeng [2 ]
机构
[1] Southern Med Univ, Sch Clin Med 1, Nanfang Hosp, Dept Crit Care Med, Guangzhou 510515, Guangdong, Peoples R China
[2] Univ South China, Peoples Hosp Chenzhou 1, Dept Crit Care Med, Inst Translat Med, Chenzhou 423000, Peoples R China
[3] Southern Med Univ, Shenzhen Hosp, Dept Anesthesiol, Shenzhen 518110, Peoples R China
[4] Fujian Med Univ, Affiliated Hosp 1, Dept Anesthesiol, Sch Clin Med 1, Fuzhou 350005, Fujian, Peoples R China
基金
中国国家自然科学基金;
关键词
FOCAL CEREBRAL-ISCHEMIA; LUNG INJURY; DYSFUNCTION; AUTOPHAGY; HYPERPERMEABILITY; MYOCARDIUM; PINK1;
D O I
10.1038/s41374-019-0191-3
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Mitophagy removes dysfunctional mitochondria and is known to play an important role in the pathogenesis of several diseases; however, the role of mitophagy in acute respiratory distress syndrome (ARDS) remains poorly understood. While we have previously demonstrated that polydatin (PD) improves lipopolysaccharide (LPS)-induced ARDS, the specific mechanism remains unclear. In present study, we aimed to determine whether PD activates Parkin-dependent mitophagy to protect against LPS-induced mitochondria-dependent apoptosis and lung injury. To establish the ARDS model, C57BL/6 mice were intratracheally injected with LPS (5 mg/kg) in vivo and Beas-2B cells were exposured to 0.5 mM LPS in vitro. Our results indicate that PD facilitates Parkin translocation to mitochondria and promotes mitophagy in ARDS-challenged mice and LPS-treated Beas-2B cells. However, PD-induced mitophagy was suppressed in Parkin-/- mice and Parkin siRNA transfected cells, indicating that PD activates Parkin-dependent mitophagy. Furthermore, the protective effects of PD against LPS-induced mitochondria-dependent apoptosis and lung injury were suppressed when Parkin was depleted both in vivo and in vitro. The inhibition of mitophagy with mitophagy inhibitor mitochondrial division inhibitor-1 in vivo and silencing of autophagy-related gene 7 in vitro also blocked the protective effects mediated by PD. Our data suggest that Parkin-dependent mitophagy induced by PD provides protection against mitochondria-dependent apoptosis in ARDS.
引用
收藏
页码:819 / 829
页数:11
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