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

• Published in: Amino acids Vol. 45; no. 2; pp. 339 - 349
• Main Authors: Ding, Fang, Yu, Lu, Wang, Meihui, Xu, Shengjie, Xia, Qiang, Fu, Guosheng
• Format: Journal Article
• Language: English
• Published: Vienna Springer-Verlag 01.08.2013; Springer Vienna; Springer Nature B.V
• Subjects: Acetylglucosamine - analogs & derivatives; Acetylglucosamine - pharmacology; Acetylglucosaminidase - antagonists & inhibitors; Acetylglucosaminidase - metabolism; Activation; Analytical Chemistry; animal disease models; Animals; Biochemical Engineering; Biochemistry; Biomedical and Life Sciences; Cardiomegaly - metabolism; cardiomyocytes; cardiomyopathy; Cyclin D2 - metabolism; cyclins; diabetes mellitus; Diabetes Mellitus, Experimental - metabolism; Enzyme Activation - drug effects; Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors; Extracellular Signal-Regulated MAP Kinases - metabolism; Flavonoids - pharmacology; gene expression; gene expression regulation; genetic markers; Glucose; Glucose - pharmacology; Glycosylation; Heart - drug effects; heart failure; hyperglycemia; hypertrophy; Inhibition; Inhibitors; JNK Mitogen-Activated Protein Kinases - metabolism; Life Sciences; Male; Markers; mitogen-activated protein kinase; Myocardium; Myocytes, Cardiac - metabolism; N-Acetylglucosaminyltransferases - genetics; N-Acetylglucosaminyltransferases - metabolism; Neurobiology; Original Article; Oximes - pharmacology; p38 Mitogen-Activated Protein Kinases - metabolism; pathogenesis; Phenylcarbamates - pharmacology; Proteins; Proteomics; Rats; Rats, Sprague-Dawley; RNA Interference; RNA, Small Interfering; Signal Transduction; small interfering RNA; Streptozocin; streptozotocin; O-GlcNAcylation; Cardiomyocyte hypertrophy; High glucose
• ISSN: 0939-4451; 1438-2199
• DOI: 10.1007/s00726-013-1504-2

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.