title: Excessive O-GlcNAcylation of proteins suppresses spontaneous cardiogenesis in ES cells.
abstract: Increased modification of proteins with O-linked N-acetylglucosamine (O-GlcNAc) has been implicated in the development of diabetic cardiomyopathy. We used the well-characterized ES cells (Nkx2.5GFP knock-in ES cells), to investigate the role of O-GlcNAcylation in cardiomyocyte development. O-GlcNAcylation decreased in differentiating ES cells, as did the expression of O-GlcNAc transferase. Increasing O-GlcNAcylation with glucosamine or by inhibiting N-acetylglucosaminidase (streptozotocin or PUGNAc) decreased the number of cardiomyocyte precursors and cardiac-specific gene expression. On the other hand, decreasing O-GlcNAcylation with an inhibitor of glutamine fructose-6-phosphate amidotransferase (6-diazo-5-oxo-norleucine) increased cardiomyocyte precursors. These results suggest that excessive O-GlcNAcylation impairs cardiac cell differentiation in ES cells.
authors: Medical Research Center, Seoul National University, Seoul, Republic of Korea. hoeskim@hotmail.com
authors: Hoe-Suk
authors: HS
authors: Kim
authors: Sang Yoon
authors: SY
authors: Park
authors: Yu Rim
authors: YR
authors: Choi
authors: Jeong Gu
authors: JG
authors: Kang
authors: Hyun Jung
authors: HJ
authors: Joo
authors: Woo Kyung
authors: WK
authors: Moon
authors: Jin Won
authors: JW
authors: Cho
mesh_terms: D000117:Acetylglucosamine / Q000031:analogs & derivatives / Q000378:metabolism*; D000118:Acetylglucosaminidase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D005260:Female; D055879:Gene Knock-In Techniques; D006321:Heart / Q000196:embryology*; D006801:Humans; D007223:Infant; D051379:Mice; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010091:Oximes / Q000378:metabolism; D048448:Phenylcarbamates / Q000378:metabolism; D013311:Streptozocin / Q000378:metabolism
chemical_list: D010091:Oximes; D048448:Phenylcarbamates; C068836:N-acetylglucosaminono-1,5-lactone O-(phenylcarbamoyl)oxime; D013311:Streptozocin; D000118:Acetylglucosaminidase; D000117:Acetylglucosamine