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

Genaro A. Ramirez-Correa, Wenhai Jin, Zihao Wang, Xin Zhong, Wei Dong Gao, Wagner B. Dias, Cecilia Vecoli, Gerald W. Hart, Anne M. Murphy

Research output: Contribution to journalArticlepeer-review

92 Scopus citations


In addition to O-phosphorylation, O-linked modifications of serine and threonine by β-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] relationships were studied in skinned rat trabeculae. Exposure to GlcNAc significantly decreased calcium sensitivity (pCa50), whereas maximal force (Fmax) 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.

Original languageEnglish (US)
Pages (from-to)1354-1358
Number of pages5
JournalCirculation research
Issue number12
StatePublished - Dec 5 2008

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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