O-linked GlcNAc modification of cardiac myofilament proteins: a novel regulator of myocardial contractile function

Circ Res. 2008 Dec 5;103(12):1354-8. doi: 10.1161/CIRCRESAHA.108.184978. Epub 2008 Nov 6.


In addition to O-phosphorylation, O-linked modifications of serine and threonine by beta-N-acetyl-D-glucosamine (GlcNAc) may regulate muscle contractile function. This study assessed the potential role of O-GlcNAcylation in cardiac muscle contractile activation. To identify specific sites of O-GlcNAcylation in cardiac myofilament proteins, a recently developed methodology based on GalNAz-biotin labeling followed by dithiothreitol replacement and light chromatography/tandem mass spectrometry site mapping was adopted. Thirty-two O-GlcNAcylated peptides from cardiac myofilaments were identified on cardiac myosin heavy chain, actin, myosin light chains, and troponin I. To assess the potential physiological role of the GlcNAc, force-[Ca(2+)] relationships were studied in skinned rat trabeculae. Exposure to GlcNAc significantly decreased calcium sensitivity (pCa50), whereas maximal force (F(max)) and Hill coefficient (n) were not modified. Using a pan-specific O-GlcNAc antibody, it was determined that acute exposure of myofilaments to GlcNAc induced a significant increase in actin O-GlcNAcylation. This study provides the first identification of O-GlcNAcylation sites in cardiac myofilament proteins and demonstrates their potential role in regulating myocardial contractile function.

Publication types

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

MeSH terms

  • Acetylglucosamine / pharmacology
  • Acetylglucosamine / physiology*
  • Actin Cytoskeleton / drug effects
  • Actin Cytoskeleton / physiology*
  • Acylation
  • Animals
  • Carbohydrate Conformation
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Contraction / drug effects
  • Myocardial Contraction / physiology*
  • Myocardium*
  • Rats


  • Acetylglucosamine