AMPK Hyper-Activation Alters Fatty Acids Metabolism and Impairs Invasiveness of Trophoblasts in Preeclampsia
Background/Aims: Preeclampsia (PE) has long been assumed to be an ischemic disease of the placenta, although there is limited evidence as to how the ischemia impacts on the placenta. AMP-activated protein kinase (AMPK) is a key regulator of cellular energy metabolism and plays an important role in a...
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Cell Physiol Biochem Press GmbH & Co KG
2018-08-01
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doaj-a222dcb253e445eea83e4047cff85d8e2020-11-25T00:53:35ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-08-0149257859410.1159/000492995492995AMPK Hyper-Activation Alters Fatty Acids Metabolism and Impairs Invasiveness of Trophoblasts in PreeclampsiaXiaotao YangPing XuFumei ZhangLi ZhangYangxi ZhengMingyu HuLulu WangTing-li HanChuan PengLianlian WangLi WenYiwen ZengRufei GaoYong XiaChao TongZhu YangHongbo QiPhilip N. BakerBackground/Aims: Preeclampsia (PE) has long been assumed to be an ischemic disease of the placenta, although there is limited evidence as to how the ischemia impacts on the placenta. AMP-activated protein kinase (AMPK) is a key regulator of cellular energy metabolism and plays an important role in a variety of ischemic diseases by enhancing energy production. The present study investigated placental metabolism in PE, and the role of AMPK in regulating trophoblast function. Methods: placentas from normal and PE complicated pregnancies were subjected to GC-MS to identify fatty acids (FA) metabolic fingerprints, and total FA oxidation was assessed by malondialdehyde (MDA) measurement. The AMPK-ACC signaling pathway was assessed by q-PCR and Western Blotting. HTR8/SVneo trophoblast cultures were exposed to different oxygenation conditions to establish an in vitro PE cell model; further analysis by GC-MS for metabolite profiling was then undertaken. Trophoblasts invasion was assessed by a matrigel transwell assay in the presence/absence of AMPK expression and after manipulations of AMPK activity, and then further validated by human villi outgrowth experiments. Results: AMPK phosphorylation and MDA production were significantly elevated in placentas from pregnancies complicated by PE. Metabolism of cis double bond FA was inhibited while trans double bond FA metabolism was promoted in PE placentas. HTR8/SVneo cell culture conditions of persistent low oxygenation mimicked the hyper-activation of AMPK and enhanced the FA oxidation that was observed in PE. AMPK activation impaired trophoblast invasion, while AMPK inhibition promoted trophoblast invasion. Conclusion: PE complicated placentas are associated with AMPK hyper-activation and consequent alterations in FA oxidation, which inhibit trophoblast invasion.https://www.karger.com/Article/FullText/492995PreeclampsiaAMPKPlacentaFatty acidsTrophoblastMetabolomics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiaotao Yang Ping Xu Fumei Zhang Li Zhang Yangxi Zheng Mingyu Hu Lulu Wang Ting-li Han Chuan Peng Lianlian Wang Li Wen Yiwen Zeng Rufei Gao Yong Xia Chao Tong Zhu Yang Hongbo Qi Philip N. Baker |
spellingShingle |
Xiaotao Yang Ping Xu Fumei Zhang Li Zhang Yangxi Zheng Mingyu Hu Lulu Wang Ting-li Han Chuan Peng Lianlian Wang Li Wen Yiwen Zeng Rufei Gao Yong Xia Chao Tong Zhu Yang Hongbo Qi Philip N. Baker AMPK Hyper-Activation Alters Fatty Acids Metabolism and Impairs Invasiveness of Trophoblasts in Preeclampsia Cellular Physiology and Biochemistry Preeclampsia AMPK Placenta Fatty acids Trophoblast Metabolomics |
author_facet |
Xiaotao Yang Ping Xu Fumei Zhang Li Zhang Yangxi Zheng Mingyu Hu Lulu Wang Ting-li Han Chuan Peng Lianlian Wang Li Wen Yiwen Zeng Rufei Gao Yong Xia Chao Tong Zhu Yang Hongbo Qi Philip N. Baker |
author_sort |
Xiaotao Yang |
title |
AMPK Hyper-Activation Alters Fatty Acids Metabolism and Impairs Invasiveness of Trophoblasts in Preeclampsia |
title_short |
AMPK Hyper-Activation Alters Fatty Acids Metabolism and Impairs Invasiveness of Trophoblasts in Preeclampsia |
title_full |
AMPK Hyper-Activation Alters Fatty Acids Metabolism and Impairs Invasiveness of Trophoblasts in Preeclampsia |
title_fullStr |
AMPK Hyper-Activation Alters Fatty Acids Metabolism and Impairs Invasiveness of Trophoblasts in Preeclampsia |
title_full_unstemmed |
AMPK Hyper-Activation Alters Fatty Acids Metabolism and Impairs Invasiveness of Trophoblasts in Preeclampsia |
title_sort |
ampk hyper-activation alters fatty acids metabolism and impairs invasiveness of trophoblasts in preeclampsia |
publisher |
Cell Physiol Biochem Press GmbH & Co KG |
series |
Cellular Physiology and Biochemistry |
issn |
1015-8987 1421-9778 |
publishDate |
2018-08-01 |
description |
Background/Aims: Preeclampsia (PE) has long been assumed to be an ischemic disease of the placenta, although there is limited evidence as to how the ischemia impacts on the placenta. AMP-activated protein kinase (AMPK) is a key regulator of cellular energy metabolism and plays an important role in a variety of ischemic diseases by enhancing energy production. The present study investigated placental metabolism in PE, and the role of AMPK in regulating trophoblast function. Methods: placentas from normal and PE complicated pregnancies were subjected to GC-MS to identify fatty acids (FA) metabolic fingerprints, and total FA oxidation was assessed by malondialdehyde (MDA) measurement. The AMPK-ACC signaling pathway was assessed by q-PCR and Western Blotting. HTR8/SVneo trophoblast cultures were exposed to different oxygenation conditions to establish an in vitro PE cell model; further analysis by GC-MS for metabolite profiling was then undertaken. Trophoblasts invasion was assessed by a matrigel transwell assay in the presence/absence of AMPK expression and after manipulations of AMPK activity, and then further validated by human villi outgrowth experiments. Results: AMPK phosphorylation and MDA production were significantly elevated in placentas from pregnancies complicated by PE. Metabolism of cis double bond FA was inhibited while trans double bond FA metabolism was promoted in PE placentas. HTR8/SVneo cell culture conditions of persistent low oxygenation mimicked the hyper-activation of AMPK and enhanced the FA oxidation that was observed in PE. AMPK activation impaired trophoblast invasion, while AMPK inhibition promoted trophoblast invasion. Conclusion: PE complicated placentas are associated with AMPK hyper-activation and consequent alterations in FA oxidation, which inhibit trophoblast invasion. |
topic |
Preeclampsia AMPK Placenta Fatty acids Trophoblast Metabolomics |
url |
https://www.karger.com/Article/FullText/492995 |
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