Impaired placental mitophagy and oxidative stress are associated with dysregulated BNIP3 in preeclampsia.
Impaired placental mitophagy and oxidative stress are associated with dysregulated BNIP3 in preeclampsia.
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胎盘线粒体自噬受损和氧化应激与先兆子痫中 BNIP3 失调相关
DOI：
10.1038/s41598-021-99837-1
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发表时间：
2021-10-14
影响因子：
4.6
通讯作者：
Baker P
中科院分区：
文献类型：
--
作者：
Zhou X;Zhao X;Zhou W;Qi H;Zhang H;Han TL;Baker P
子痫前期（PE）是一种严重的多系统妊娠并发症，以妊娠期高血压和蛋白尿为特征。Bcl-2/腺病毒E1B 19kda相互作用蛋白3 （BNIP3）是一种线粒体自噬的介质，已被证明与PE相关，但其机制尚不清楚。本研究旨在探讨BNIP3在PE中的作用。采用western-blot和透射电镜对子痫前期和正常妊娠胎盘进行分析，定量测定BNIP3的表达水平并观察细胞器形态。用western-blot、免疫荧光、流式细胞术、迁移和侵袭等方法分析敲低BNIP3的滋养细胞。PE患者BNIP3表达受到抑制。与正常胎盘相比，PE胎盘的自噬功能受损，线粒体损伤增加。抑制BNIP3抑制Beclin-1表达，减少LC3-I向LC3-II的转化。在BNIP3敲低组，氧化应激条件下p62过表达，ROS积累，凋亡过程升高。BNIP3的敲低降低了GFP-LC3和线粒体的共定位。本研究结果表明，BNIP3失调与PE中线粒体自噬受损、氧化应激和细胞凋亡有关。该研究为BNIP3在PE病理生理中的作用提供了新的见解。
Preeclampsia (PE) is a severe multisystem pregnancy complication characterized by gestational hypertension and proteinuria. Bcl-2/adenovirus E1B 19-kDa interacting protein 3 (BNIP3) is a mediator of mitophagy and has been proven to be associated with PE, but the mechanism is not well understood. This study aimed to investigate the role of BNIP3 in PE. Placentae from preeclamptic and normal pregnancies were analyzed by western-blot and transmission electron microscopy to quantify the level of BNIP3 expression and observe the organelle morphologies. Trophoblast cells with knockdown BNIP3 were analyzed by western-blot, immunofluorescence, flow cytometry, migration and invasion assays. BNIP3 expression was suppressed in PE patients. Impaired autophagy and increased mitochondrial damage were observed in PE placentae when compared with normal placentae. Suppression of BNIP3 inhibited Beclin-1 expression and reduced the transformation of LC3-I to LC3-II. In the knockdown BNIP3 group, p62 was overexpressed, ROS accumulated and the apoptotic process was elevated under oxidative stress condition. The knockdown of BNIP3 reduced the colocalization of GFP-LC3 and mitochondria. The findings of this study suggest that dysregulated BNIP3 is associated with impaired mitophagy, oxidative stress, and apoptosis in PE. The study provides new insights into the role of BNIP3 in the pathophysiology of PE.
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影响因子：
4.6
作者：
Arikawa T;Liao S;Shimada H;Inoue T;Sakata-Haga H;Nakamura T;Hatta T;Shoji H
通讯作者：
Shoji H
影响因子：
6.2
作者：
Kamino H;Nakamura Y;Tsuneki M;Sano H;Miyamoto Y;Kitamura N;Futamura M;Kanai Y;Taniguchi H;Shida D;Kanemitsu Y;Moriya Y;Yoshida K;Arakawa H
通讯作者：
Arakawa H
影响因子：
16
作者：
Kroemer G;Mariño G;Levine B
通讯作者：
Levine B
DOI：
10.1073/pnas.1706546114
发表时间：
2017-10-03
影响因子：
11.1
作者：
Garrido-Gomez, Tamara;Dominguez, Francisco;Simon, Carlos
通讯作者：
Simon, Carlos
影响因子：
32.4
作者：
Larson-Casey JL;Deshane JS;Ryan AJ;Thannickal VJ;Carter AB
通讯作者：
Carter AB