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Ursodeoxycholyl lysophosphatidylethanolamide protects against hepatic ischemia/reperfusion injury via phospholipid metabolism‐mediated mitochondrial quality control
Author(s) -
Gu Jian,
Zhang Tao,
Guo Jianrong,
Chen Ke,
Wang Guobin,
Li Huili,
Wang Jiliang
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201902013rrr
Subject(s) - mitochondrion , phospholipid , oxidative stress , phospholipase a2 , apoptosis , lipid metabolism , reactive oxygen species , biology , reperfusion injury , biochemistry , microbiology and biotechnology , chemistry , ischemia , medicine , enzyme , membrane
Mitochondrial dysfunction is the leading cause of reactive oxygen species (ROS) burst and apoptosis in hepatic ischemia/reperfusion (I/R) injury. Ursodeoxycholyl lysophosphatidylethanolamide (UDCA‐LPE) is a hepatotargeted agent that exerts hepatoprotective roles by regulating lipid metabolism. Our previous studies have shown that UDCA‐LPE improves hepatic I/R injury by inhibiting apoptosis and inflammation. However, the role of UDCA‐LPE in lipid metabolism and mitochondrial function in hepatic I/R remains unknown. In the present study, we investigated the role of UDCA‐LPE in hepatic I/R by focusing on the interface of phospholipid metabolism and mitochondrial homeostasis. Livers from 28‐week‐old mice, primary hepatocytes and HepG2 cells were subjected to in vivo and in vitro I/R, respectively. Analyses of oxidative stress, imaging, ATP generation, genetics, and lipidomics showed that I/R was associated with mitochondrial dysfunction and a reduction in phospholipids. UDCA‐LPE alleviated mitochondria‐dependent oxidative stress and apoptosis and prevented the decrease of phospholipid levels. Our study found that cytosolic phospholipase A 2 (cPLA 2 ), a phospholipase that is activated during I/R, hydrolyzed mitochondrial membrane phospholipids and led to mitochondria‐mediated oxidative stress and apoptosis. UDCA‐LPE inhibited the interaction between cPLA 2 and mitochondria and reduced phospholipid hydrolysis‐mediated injury. UDCA‐LPE might regulate the crosstalk between the phospholipid metabolism and the mitochondria, restore mitochondrial function and ameliorate I/R injury.