Excessive O-GlcNAcylation of proteins suppresses spontaneous cardiogenesis in ES cells

Excessive O-GlcNAcylation of proteins suppresses spontaneous cardiogenesis in ES cells
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DOI:
10.1016/j.febslet.2009.06.052
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发表时间:
2009-08-06
期刊:
影响因子:
3.5
通讯作者:
Cho, Jin Won
Cho, Jin Won
中科院分区:
生物学3区
文献类型:
--
作者:
Kim, Hoe-Suk;Park, Sang Yoon;Cho, Jin Won

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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. (c) 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.