共 34 条
Polydatin mediates Parkin-dependent mitophagy and protects against mitochondria-dependent apoptosis in acute respiratory distress syndrome
被引:51
作者:

Li, Tao
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机构:
Southern Med Univ, Sch Clin Med 1, Nanfang Hosp, Dept Crit Care Med, Guangzhou 510515, Guangdong, Peoples R China
Univ South China, Peoples Hosp Chenzhou 1, Dept Crit Care Med, Inst Translat Med, Chenzhou 423000, Peoples R China Southern Med Univ, Sch Clin Med 1, Nanfang Hosp, Dept Crit Care Med, Guangzhou 510515, Guangdong, Peoples R China

Liu, Youtan
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h-index: 0
机构:
Southern Med Univ, Shenzhen Hosp, Dept Anesthesiol, Shenzhen 518110, Peoples R China Southern Med Univ, Sch Clin Med 1, Nanfang Hosp, Dept Crit Care Med, Guangzhou 510515, Guangdong, Peoples R China

Xu, Wei
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机构:
Southern Med Univ, Sch Clin Med 1, Nanfang Hosp, Dept Crit Care Med, Guangzhou 510515, Guangdong, Peoples R China Southern Med Univ, Sch Clin Med 1, Nanfang Hosp, Dept Crit Care Med, Guangzhou 510515, Guangdong, Peoples R China

Dai, Xingui
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h-index: 0
机构:
Univ South China, Peoples Hosp Chenzhou 1, Dept Crit Care Med, Inst Translat Med, Chenzhou 423000, Peoples R China Southern Med Univ, Sch Clin Med 1, Nanfang Hosp, Dept Crit Care Med, Guangzhou 510515, Guangdong, Peoples R China

Liu, Ruimeng
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Southern Med Univ, Shenzhen Hosp, Dept Anesthesiol, Shenzhen 518110, Peoples R China Southern Med Univ, Sch Clin Med 1, Nanfang Hosp, Dept Crit Care Med, Guangzhou 510515, Guangdong, Peoples R China

Gao, Youguang
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h-index: 0
机构:
Fujian Med Univ, Affiliated Hosp 1, Dept Anesthesiol, Sch Clin Med 1, Fuzhou 350005, Fujian, Peoples R China Southern Med Univ, Sch Clin Med 1, Nanfang Hosp, Dept Crit Care Med, Guangzhou 510515, Guangdong, Peoples R China

Chen, Zhongqing
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h-index: 0
机构:
Southern Med Univ, Sch Clin Med 1, Nanfang Hosp, Dept Crit Care Med, Guangzhou 510515, Guangdong, Peoples R China Southern Med Univ, Sch Clin Med 1, Nanfang Hosp, Dept Crit Care Med, Guangzhou 510515, Guangdong, Peoples R China

Li, Yunfeng
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h-index: 0
机构:
Univ South China, Peoples Hosp Chenzhou 1, Dept Crit Care Med, Inst Translat Med, Chenzhou 423000, Peoples R China Southern Med Univ, Sch Clin Med 1, Nanfang Hosp, Dept Crit Care Med, Guangzhou 510515, Guangdong, Peoples R China
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.
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收藏
页码:819 / 829
页数:11
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TOXICOLOGY,
2015, 334
:72-80

Dai, Hongmei
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Cent S Univ, Dept Pediat, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China Cent S Univ, Dept Pediat, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China

Deng, Yuanying
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Cent S Univ, Dept Pediat, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China Cent S Univ, Dept Pediat, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China

Zhang, Jie
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机构:
Cent S Univ, Dept Neurol, Xiangya Hosp 2, Changsha 410013, Hunan, Peoples R China Cent S Univ, Dept Pediat, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China

Han, Hailong
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机构:
Cent S Univ, State Key Lab Med Genet, Changsha 410013, Hunan, Peoples R China Cent S Univ, Dept Pediat, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China

Zhao, Mingyi
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Cent S Univ, Dept Pediat, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China Cent S Univ, Dept Pediat, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China

Li, Ying
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Cent S Univ, Dept Pediat, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China Cent S Univ, Dept Pediat, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China

Zhang, Chen
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Cent S Univ, Dept Pediat, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China Cent S Univ, Dept Pediat, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China

Tian, Jing
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Cent S Univ, Dept Pediat, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China Cent S Univ, Dept Pediat, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China

Bing, Guoying
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机构:
Univ Kentucky, Sch Med, Dept Anat & Neurobiol, Lexington, KY 40536 USA Cent S Univ, Dept Pediat, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China

Zhao, Lingling
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Cent S Univ, Dept Pediat, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China Cent S Univ, Dept Pediat, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China