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O-GlcNAcylation involvement in high glucose-induced cardiac hypertrophy via ERK1/2 and cyclin D2

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Abstract

Continuous hyperglycemia is considered to be the most significant pathogenesis of diabetic cardiomyopathy, which manifests as cardiac hypertrophy and subsequent heart failure. O-GlcNAcylation has attracted attention as a post-translational protein modification in the past decade. The role of O-GlcNAcylation in high glucose-induced cardiomyocyte hypertrophy remains unclear. We studied the effect of O-GlcNAcylation on neonatal rat cardiomyocytes that were exposed to high glucose and myocardium in diabetic rats induced by streptozocin. High glucose (30 mM) incubation induced a greater than twofold increase in cell size and increased hypertrophy marker gene expression accompanied by elevated O-GlcNAcylation protein levels. High glucose increased ERK1/2 but not p38 MAPK or JNK activity, and cyclin D2 expression was also increased. PUGNAc, an inhibitor of β-N-acetylglucosaminidase, enhanced O-GlcNAcylation and imitated the effects of high glucose. OGT siRNA and ERK1/2 inhibition with PD98059 treatment blunted the hypertrophic response and cyclin D2 upregulation. OGT inhibition also prevented ERK1/2 activation. We also observed concentric hypertrophy and similar changes of O-GlcNAcylation level, ERK1/2 activation and cyclin D2 expression in myocardium of diabetic rats induced by streptozocin. In conclusion, O-GlcNAcylation plays a role in high glucose-induced cardiac hypertrophy via ERK1/2 and cyclin D2.

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Acknowledgments

We thank the Biomedical Research Center in Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, for the use of instruments and equipment.

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Authors and Affiliations

  1. Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, No. 3 Qingchun East Road, Hangzhou, 310016, Zhejiang, China

    Fang Ding, Lu Yu, Meihui Wang, Shengjie Xu & Guosheng Fu

  2. The Province Center for Cardio-Cerebral-Vascular Disease, Zhejiang Hospital, Hangzhou, Zhejiang, China

    Fang Ding

  3. Department of Physiology, College of Medicine, Zhejiang University, No 866 Yuhangtang Road, Hangzhou, 310058, Zhejiang, China

    Qiang Xia

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  1. Fang Ding
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  2. Lu Yu
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  3. Meihui Wang
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Correspondence to Qiang Xia or Guosheng Fu.

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Ding, F., Yu, L., Wang, M. et al. O-GlcNAcylation involvement in high glucose-induced cardiac hypertrophy via ERK1/2 and cyclin D2. Amino Acids 45, 339–349 (2013). https://doi.org/10.1007/s00726-013-1504-2

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