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.
Bibliographical noteFunding Information:
This work was supported by a Korea Research Foundation Grant funded by the Korean Government (MOEHRD; KRF-2006-311-C00399), grants from the Korea Science and Engineering Foundation (KOSEF) funded by the Ministry of Education, Science and Technology Grant (R0A-2007-000-20011-0), Korea Research Foundation Grant (KRF-2004-005-C00112) and WCU project (R31-2008-000-10086-0). S.Y.P. and J.G.K. are fellowship awardees of the Brain Korea 21 (BK21) program. This work was made possible through the use of research facilities in the Yonsei Center for Biotechnology. We thank Dr. T. Morisaki and K. Hidaka (National Cardiovascular Center Research Institute at Osaka, Japan) for providing mouse embryonic stem cell line.
All Science Journal Classification (ASJC) codes
- Structural Biology
- Molecular Biology
- Cell Biology