The Mechanism Of Mitochondria-related Apoptosis Induced By FAM134B-mediated Endoplasmic Reticulum Autophagy In The Pathogenesis Of Preeclampsia

Objective: The pathogenesis of preeclampsia is often associated with placental oxidative stress and apoptosis.The purpose of this study was to elucidate the expression of the endoplasmic reticulum autophagy marker protein FAM134B(Family with sequence similarity 134,member B)in placental tissue and trophoblasts and the mitochondria induced by calcium channel dysfunction in the mitochondria-associated endoplasmic reticulum membrane.Role of related apoptosis in preeclampsia(PE).Methods: Eight cases of PE and eight cases of normal placenta were delivered from the Department of Obstetrics,the First Affiliated Hospital of Chongqing Medical University from September 2017 to December 2017.The expression of FAM134 B,IP3R and Cytochrome C in PE and normal placenta was detected by Western blot.The positive expression of FAM134 B and IP3 R in placenta was detected by immunohistochemistry.The PE cell model was constructed by using SNP(Sodium nitroprusside)in HTR8/SVneo cells and make the FAM134 B lentiviral transfected cell model.The expression of FAM134 B in the endoplasmic reticulum was detected by immunofluorescence and laser confocal microscopy.Western blot(WB)was used to detect the effect of mitochondrial-related apoptosis after the knockdown and overexpression of FAM134 B.The apoptosis rateof the three groups was detected by flow cytometry(FC).Results: Western blotting results showed that the expression of endoplasmic reticulum autophagy(ER-Phagy)protein FAM134 B,calcium channel protein IP3 R and mitochondrial apoptosis protein Cytochrome C was significantly increased in PE placenta tissue compared with normal placenta(p<0.05);immunohistochemistry results found that the expression of FAM134 B and IP3 R in the endoplasmic reticulum(ER)of the PE group was significantly increased(p<0.001).The results of Western blotting demonstrated that the expression of FAM134 B,IP3R and Cytochrome C protein in SNP-induced PE cell model was significantly higher than HTR8/SVneo cells(p<0.01).Western blotting and flow cytometry investigated increased mitochondrial apoptosis in HTR8/SVneo cells after knockdown and overexpression of FAM134 B in HTR8/SVneo cells(p<0.05).Conclusion: FAM134 B mediated endoplasmic reticulum autophagy leads to increased apoptosis through mitochondria-associated endoplasmic reticulum membrane,causing dysfunction of trophoblast cells and participating in the pathogenesis of PE.