Activating Parkin-dependent mitophagy alleviates oxidative stress, apoptosis, and promotes random-pattern skin flaps survival

被引:40
作者
Chen, Zhengtai [1 ,2 ]
Wu, Hongqiang [1 ,2 ]
Yang, Jianxin [1 ,2 ]
Li, Baolong [1 ,2 ]
Ding, Jian [1 ,2 ]
Cheng, Sheng [1 ,2 ]
Bsoul, Nageeb [1 ,3 ]
Zhang, Chenxi [4 ]
li, Jiaorong [3 ]
Liu, Haixiao [1 ,2 ]
Lin, Damu [1 ]
Gao, Weiyang [1 ,2 ]
机构
[1] Wenzhou Med Univ, Affiliated Hosp & Yuying Childrens Hosp 2, Dept Orthoped, Wenzhou 325000, Zhejiang, Peoples R China
[2] Zhejiang Prov Key Lab Orthoped, Wenzhou 325000, Zhejiang, Peoples R China
[3] Wenzhou Med Univ, Wenzhou, Peoples R China
[4] 6 Hosp Ningbo, Dept Orthoped, Ningbo, Peoples R China
关键词
ISCHEMIA-REPERFUSION INJURY; MITOCHONDRIA; MELATONIN; AUTOPHAGY; TFEB; NEUTROPHILS; CROSSROAD; PROTECTS; DISEASE; MODEL;
D O I
10.1038/s42003-022-03556-w
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The random-pattern skin flap is a crucial technique in reconstructive surgery and flap necrosis caused by ischemia/reperfusion injury is a major postoperative complication. Herein, we investigated the mechanism of mitophagy induced by Melatonin (ML) and its effect on the survival of skin flaps. Our results demonstrated that ML could activate mitophagy, ameliorate oxidative stress and alleviate apoptosis in Tert-Butyl hydroperoxide solution (TBHP)-stimulated human umbilical vein endothelial cells in vitro. Inhibiting ML-induced mitophagy considerably abolished its protective effects. Moreover, knockdown of Parkin by siRNA inhibited ML-induced mitophagy, and subsequently exacerbated oxidative stress and apoptosis. Further study demonstrated that inhibition of AMPK reversed these protective effects of ML and downregulated the expression of TFEB. In the vivo study, ML effectively promoted flap survival by activating mitophagy and subsequently ameliorating oxidative stress and mitigating apoptosis. These results established that ML is a potent agent capable for increasing random-pattern skin flap survival by activating Parkin-dependent mitophagy through the AMPK-TFEB signaling pathway. Melatonin induces Parkin 1 dependent mitophagy in human umbilical vein endothelial cells through the AMPK/TFEB pathway, alleviating oxidative stress and apoptosis, which also enables skin flap survival in vivo.
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页数:14
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