Cardiac transcription factor Nkx2.5 is downregulated under excessive O-GlcNAcylation condition.
Post-translational modification of proteins with O-linked N-acetylglucosamine (O-GlcNAc) is linked the development of diabetic cardiomyopathy. We investigated whether Nkx2.5 protein, a cardiac transcription factor, is regulated by O-GlcNAc. Recombinant Nkx2.5 (myc-Nkx2.5) proteins were reduced by treatment with the O-GlcNAcase inhibitors STZ and O-(2-acetamido-2-deoxy-D-glucopyroanosylidene)-amino-N-phenylcarbamate; PUGNAC) as well as the overexpression of recombinant O-GlcNAc transferase (OGT-flag). Co-immunoprecipitation analysis revealed that myc-Nkx2.5 and OGT-flag proteins interacted and myc-Nkx2.5 proteins were modified by O-GlcNAc. In addition, Nkx2.5 proteins were reduced in the heart tissue of streptozotocin (STZ)-induced diabetic mice and O-GlcNAc modification of Nkx2.5 protein increased in diabetic heart tissue compared with non-diabetic heart. Thus, excessive O-GlcNAcylation causes downregulation of Nkx2.5, which may be an underlying contributing factor for the development of diabetic cardiomyopathy.
The Institute of Radiation Medicine, Medical Research Center, Seoul National University, Jongno-gu, Seoul, Korea.
Hoe Suk
HS
Kim
Ji Soo
JS
Woo
Hyun Jung
HJ
Joo
Woo Kyung
WK
Moon
D000117:Acetylglucosamine / Q000378:metabolism*; D000215:Acylation; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D015536:Down-Regulation; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D013311:Streptozocin; D014157:Transcription Factors / Q000378:metabolism*
D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C484469:Nkx2-5 protein, mouse; D014157:Transcription Factors; D013311:Streptozocin; D000117:Acetylglucosamine