Impaired Mitophagy Induced By BNIP3 Is Involved In The Development Of Preeclampsia

Objective:To characterize the expression of BCL2/adenovirus E1B19 k Da protein-interacting protein 3(BNIP3)in placenta and mitophagy induced by BNIP3 in regulation of function of trophoblasts in preeclampsia(PE).Methods: Placental tissues from 11 cases of severe preeclampsia(PE)and 12 cases of normal pregnancies were collected in the First Affiliated Hospital of Chongqing Medical University from January 2015 to August2015.The expressions of BNIP3 and cleaved-caspase3 protein were detected in placentas from normal pregnancies and pregnancies complicated with PE by Western blot.Mitochondria were isolated and analyzed by Gas chromatograph-mass spectrometer(GC-MS).Luciferase-luciferin reaction assay was used to quantify the ATP levels.HTR8/SVneo was used as the PE cell model and treated with hypoxia/reoxygenation(H/R).RNA interference technology was performed by using BNIP3 specific small interfering RNA(si RNA);Western blot was used to identify the expression of BNIP3 after RNA interference.Invasionwas detected by Transwell assay.The experiments were divided into two groups: si-NC group and si-BNIP3 group,then treated with H/R,the production of ROS within cells was detected by 2',7'-dichlorodi-hydro-fluorescein diacetate(DCFH-DA)and flow cytometry was used to detect the apoptotic cells.Results: The expression of BNIP3 in placentas from PE was lower and the expression of cleaved-caspase3 was higher.The GC-MS analysis demonstrated that the activities of mitochondria in PE placentas were inhibited.ATP levels in the placentas from the PE group were substantially decreased compared to the standard group.Within the PE cell model,the knock-down of BNIP3 by si RNA significantly increased the production of ROS,activities of apoptosis in HTR8/SVneo and decreased invasion abilities.Conclusion: Impaired mitophagy induced by BNIP3 within placenta participates in the excessive production of ROS,shallow invasion and excessive apoptosis in PE.