Enhanced cardiac protein glycosylation (O-GlcNAc) of selected mitochondrial proteins in rats artificially selected for low running capacity

Physiol Genomics. 2013 Jan 7;45(1):17-25. doi: 10.1152/physiolgenomics.00111.2012. Epub 2012 Nov 6.

Abstract

O-linked β-N-acetyl glucosamine (O-GlcNAc) is a posttranslational modification consisting of a single N-acetylglucosamine moiety attached by an O-β-glycosidic linkage to serine and threonine residues of both nuclear and cytosolic proteins. Analogous to phosphorylation, the modification is reversible and dynamic, changing in response to stress, nutrients, hormones, and exercise. Aims of this study were to examine differences in O-GlcNAc protein modification in the cardiac tissue of rats artificially selected for low (LCR) or high (HCR) running capacity. Hyperinsulinemic-euglycemic clamps in conscious animals assessed insulin sensitivity while 2-[(14)C] deoxyglucose tracked both whole body and tissue-specific glucose disposal. Immunoblots of cardiac muscle examined global O-GlcNAc modification, enzymes that control its regulation (OGT, OGA), and specific proteins involved in mitochondrial oxidative phosphorylation. LCR rats were insulin resistant disposing of 65% less glucose than HCR. Global tissue O-GlcNAc, OGT, OGA, and citrate synthase were similar between groups. Analysis of cardiac proteins revealed enhanced O-GlcNAcylation of mitochondrial Complex I, Complex IV, VDAC, and SERCA in LCR compared with HCR. These results are the first to establish an increase in specific protein O-GlcNAcylation in LCR animals that may contribute to progressive mitochondrial dysfunction and the pathogenesis of insulin resistance observed in the LCR phenotype.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Analysis of Variance
  • Animals
  • Carbon Radioisotopes / metabolism
  • Citrate (si)-Synthase / metabolism
  • Fatty Acids, Nonesterified / blood
  • Glucose / metabolism
  • Glucose Clamp Technique / methods
  • Glycosylation
  • Immunoblotting
  • Insulin Resistance / physiology*
  • Kinetics
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism*
  • Models, Animal*
  • Myocardium / metabolism*
  • N-Acetylglucosaminyltransferases / metabolism
  • Oxidative Phosphorylation
  • Rats
  • Rats, Inbred Strains
  • Running / physiology*

Substances

  • Carbon Radioisotopes
  • Fatty Acids, Nonesterified
  • Mitochondrial Proteins
  • Citrate (si)-Synthase
  • N-Acetylglucosaminyltransferases
  • UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase
  • Glucose