Impact of protein O-GlcNAcylation on neural tube malformation in diabetic embryopathy.

ABSTRACT: Diabetes 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 preg

SUBMITTER: Kim G 

PROVIDER: S-EPMC5593976 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature