The Study Of Hyper-activation Of AMPK In Preeclampsia

Preeclampsia(PE)is characterized by compromised trophoblast invasion and consequent inadequate placental perfusion,and has thus been proposed to be an ischemic placental disease.However,the metabolic response to ischemia of trophoblast cells and the consequent effect on mobility remain unclear.In the present study,we found abnormal AMPK activation and enhanced GLUT3 trafficking from cytoplasm to plasma membrane in placenta from human pregnancies complicated by PE and trophoblast cells in conditions of hypoxia.AMPK activation not only impaired trophoblast invasion,but also suppressed activity of MMPs and apoptotic signaling.In contrast,inhibition of AMPK promoted trophoblast invasion and MMPs activity,as well as apoptosis.The homeostasis between invasiveness and viability of trophoblast was further confirmed by comparing first trimester human villi to term placenta.Although activation of AMPK increased glucose uptake into trophoblast cells,metabolomic profiling demonstrated that glucose taken up by AMPK in trophoblast was not metabolized through either oxidative phosphorylation nor lactate fermentation,but resulted inaccumulation of phosphoenolpyruvate,which is known to enhance growth and proliferation in cancer cells.Moreover,the fatty acid metabolism in preeclampsia placenta has been significantly changed,which not only preserves the cis double bonds of fatty acids,reduces the fatty acid trans double bonds,but also reduces the medium chain fatty acids and increases the accumulation of long chain fatty acids.The present study is the first report of the disturbed balance between invasion and viability due to trophoblast AMPK hyper-activation in PE.