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dc.contributor.authorKim, G.
dc.contributor.authorCao, L.
dc.contributor.authorReece, E.A.
dc.date.accessioned2019-10-08T19:43:53Z
dc.date.available2019-10-08T19:43:53Z
dc.date.issued2017
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85029230465&doi=10.1038%2fs41598-017-11655-6&partnerID=40&md5=e23432109f6f8357eeebfb85043898e5
dc.identifier.urihttp://hdl.handle.net/10713/11132
dc.description.abstractDiabetes mellitus in early pregnancy can cause neural tube defects (NTDs) in embryos by perturbing protein activity, causing cellular stress, and increasing programmed cell death (apoptosis) in the tissues required for neurulation. Hyperglycemia augments a branch pathway in glycolysis, the hexosamine biosynthetic pathway (HBP), to increase uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc). GlcNAc can be added to proteins by O-GlcNAc transferase (OGT) to regulate protein activity. In the embryos of diabetic mice, OGT is highly activated in association with increases in global protein O-GlcNAcylation. In neural stem cells in vitro, high glucose elevates O-GlcNAcylation and reactive oxygen species, but the elevations can be suppressed by an OGT inhibitor. Inhibition of OGT in diabetic pregnant mice in vivo decreases NTD rate in the embryos. This effect is associated with reduction in global O-GlcNAcylation, alleviation of intracellular stress, and decreases in apoptosis in the embryos. These suggest that OGT plays an important role in diabetic embryopathy via increasing protein O-GlcNAcylation, and that inhibiting OGT could be a candidate approach to prevent birth defects in diabetic pregnancies. Copyright 2017 The Author(s).en_US
dc.description.sponsorshipThe authors thank Hua Li for technical assistance, Dr. Min Zhan for statistical analyses, and Dr. Julie Rosen for critical reading and editing. The work was supported by the National Institutes of Health under Award Numbers HD076245 and HD075995.en_US
dc.description.urihttps://www.ncbi.nlm.nih.gov/pubmed/?term=Impact+of+protein+O-GlcNAcylation+on+neural+tube+malformation+in+diabetic+embryopathyen_US
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofScientific Reports
dc.subject.meshAcetylglucosamine--metabolismen_US
dc.subject.meshDiabetes Complicationsen_US
dc.subject.meshMaternal Exposureen_US
dc.subject.meshNeural Tube Defectsen_US
dc.subject.meshProtein Processing, Post-Translationalen_US
dc.titleImpact of protein O-GlcNAcylation on neural tube malformation in diabetic embryopathyen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41598-017-11655-6
dc.identifier.pmid28894244


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