安普克
滋养层
胎盘形成
胎盘
糖原
糖异生
生物
活力测定
碳水化合物代谢
细胞生物学
内分泌学
化学
内科学
新陈代谢
蛋白激酶A
生物化学
细胞
激酶
医学
胎儿
遗传学
怀孕
作者
Ping Xu,Yaqiu Zheng,Jiujiang Liao,Mingyu Hu,Yong Yang,Baozhen Zhang,Mark D. Kilby,Huijia Fu,Yamin Liu,Fumei Zhang,Liling Xiong,Xiyao Liu,Huili Jin,Yue Wu,Jiayu Huang,Ting‐Li Han,Wen Li,Rufei Gao,Yong Fu,Xiujun Fan,Hongbo Qi,Philip N. Baker,Chao Tong
摘要
Pre-eclampsia (PE) is deemed an ischemia-induced metabolic disorder of the placenta due to defective invasion of trophoblasts during placentation; thus, the driving role of metabolism in PE pathogenesis is largely ignored. Since trophoblasts undergo substantial glycolysis, this study aimed to investigate its function and regulatory mechanism by AMPK in PE development. Metabolomics analysis of PE placentas was performed by gas chromatography-mass spectrometry (GC-MS). Trophoblast-specific AMPKα1-deficient mouse placentas were generated to assess morphology. A mouse PE model was established by Reduced Uterine Perfusion Pressure, and placental AMPK was modulated by nanoparticle-delivered A769662. Trophoblast glucose uptake was measured by 2-NBDG and 2-deoxy-d-[3 H] glucose uptake assays. Cellular metabolism was investigated by the Seahorse assay and GC-MS.PE complicated trophoblasts are associated with AMPK hyperactivation due not to energy deficiency. Thereafter, AMPK activation during placentation exacerbated PE manifestations but alleviated cell death in the placenta. AMPK activation in trophoblasts contributed to GLUT3 translocation and subsequent glucose metabolism, which were redirected into gluconeogenesis, resulting in deposition of glycogen and accumulation of phosphoenolpyruvate; the latter enhanced viability but compromised trophoblast invasion. However, ablation of AMPK in the mouse placenta resulted in decreased glycogen deposition and structural malformation. These data reveal a novel homeostasis between invasiveness and viability in trophoblasts, which is mechanistically relevant for switching between the 'go' and 'grow' cellular programs.
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