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O-GlcNAc cycling enzymes control vascular development of the placenta by modulating the levels of HIF-1α

Author(s)
Yang, Yong RyoulJang, Hyun-JunLee, Yong HwaKim, Il ShinLee, HoRyu, Sung HoSuh, Pann-Ghill
Issued Date
2015-10
DOI
10.1016/j.placenta.2015.08.001
URI
https://scholarworks.unist.ac.kr/handle/201301/16802
Fulltext
http://www.sciencedirect.com/science/article/pii/S014340041530028X
Citation
PLACENTA, v.36, pp.1063 - 1068
Abstract
Introduction: Placental vasculogenesis is essential for fetal growth and development, and is affected profoundly by oxygen tension (hypoxia). Hypoxia-inducible factor-1 alpha: (HIF-1 alpha), which is stabilized at the protein level in response to hypoxia, is essential for vascular morphogenesis in the placenta. Many studies suggested that responses to hypoxia is influenced by O-GlcNAcylation. O-GlcNAcylation is regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) that catalyze the addition and removal of O-GlcNAc respectively.

Methods: We generated OGA deficient mice and evaluated OGA(-/-) placentas. The analysis of OGA(-/-) placentas was focused on morphological change and placental vasculogenesis. HIF-1 alpha: protein stability or transcriptional activity under dysregulation of O-GlcNAcylation were evaluated by Western blot, RT-qPCR and luciferase reporter gene assays in MEFs or MS1 cell line.

Results: Deletion of OGA results in defective placental vasculogenesis. OGA(-/-) placentas showed an abnormal placental shape and reduced vasculature in the labyrinth, which caused a developmental delay in the embryos. OGA deletion, which elevates O-GlcNAcylation and downregulates O-GlcNAc transferase (OGT), suppressed HIF-1 alpha stabilization and the transcription of its target genes. In contrast, the overexpression of O-GlcNAc cycling enzymes enhanced the expression and transcriptional activity of HIF-1 alpha.

Discussion: These results suggest that OGA plays a critical role in placental vasculogenesis by modulating HIP-1 alpha stabilization. Control of O-GlcNAcylation is essential for placental development. (C) 2015 Elsevier Ltd. All rights reserved.
Publisher
W B SAUNDERS CO LTD
ISSN
0143-4004
Keyword (Author)
O-GlcNAcylationOGAOGTPlacentaVasculogenesisHIF-1 alphaHypoxia
Keyword
HYPOXIASTRESSCELLSGLCNACYLATIONDYSFUNCTIONPHOSPHORYLATIONTRANSCRIPTIONTRANSFERASEHOMEOSTASISPATHWAY

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