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

Kim, Hoe-Suk; Park, Sang Yoon; Choi, Yu Rim; Kang, Jeong Gu; Joo, Hyun Jung; Moon, Woo Kyung; Cho, Jin Won

doi:10.1016/j.febslet.2009.06.052

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Volume 583, Issue 15 , Pages 2474-2478, 6 August 2009

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

Edited by Laszlo Nagy

Hoe-Suk Kim
- Medical Research Center, Seoul National University, 101 Daehangno, Jongno-gu, Seoul 110-744, Republic of Korea
- Department of Diagnostic Radiology, Seoul National University Hospital, 101 Daehangno, Jongno-gu, Seoul 110-744, Republic of Korea
- Corresponding authors. Address: Medical Research Center, Seoul National University, Daehangno, Jongno-gu, Seoul 110-744, Republic of Korea. Fax: +82 2 743 6385 (H.-S. Kim).
- These authors contributed equally to this work.
Sang Yoon Park
- Department of Biology and WCU Program Department of Biomedical Science, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749, Republic of Korea
- These authors contributed equally to this work.
Yu Rim Choi
- Medical Research Center, Seoul National University, 101 Daehangno, Jongno-gu, Seoul 110-744, Republic of Korea
Jeong Gu Kang
- Department of Biology and WCU Program Department of Biomedical Science, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749, Republic of Korea
Hyun Jung Joo
- Department of Diagnostic Radiology, Seoul National University Hospital, 101 Daehangno, Jongno-gu, Seoul 110-744, Republic of Korea
Woo Kyung Moon
- Department of Diagnostic Radiology, Seoul National University Hospital, 101 Daehangno, Jongno-gu, Seoul 110-744, Republic of Korea
Jin Won Cho
- Department of Biology and WCU Program Department of Biomedical Science, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749, Republic of Korea
- Corresponding authors. Address: Medical Research Center, Seoul National University, Daehangno, Jongno-gu, Seoul 110-744, Republic of Korea. Fax: +82 2 743 6385 (H.-S. Kim).

Received 15 May 2009; received in revised form 18 June 2009; accepted 26 June 2009. published online 08 July 2009.

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.

Keywords: O-linked N-acetylglucosamine, Embryonic stem cell, Cardiogenesis, Nkx2.5 transcription factor, Diabetes, O-GlcNAcylation