Myosin binding protein C is differentially phosphorylated upon myocardial stunning in canine and rat hearts - Evidence for novel phosphorylation sites

Chao Yuan, Yurong Guo, Rajashree Ravi, Karin Przyklenk, Nicole Shilkofski, Roberto Diez, Robert N. Cole, Anne M. Murphy

Research output: Contribution to journalArticle

Abstract

Myocardial stunning is the transient cardiac dysfunction that follows brief episodes of ischemia and reperfusion without associated myocardial necrosis. Currently, there is limited knowledge about its cellular and biochemical mechanisms. In order to better understand the underlying mechanisms of contractile dysfunction associated with the stunning, comprehensive proteomic studies using 2-D DIGE were performed using a regional stunning model in canine heart. Cardiac myosin binding protein C (cMyBP-C), a regulatory myofilament protein associated with the thick filament, and nebulette, a thin filament associated protein, were differentially expressed. Phosphoprotein specific staining indicated both protein changes were due to phosphorylation. Subsequent phosphorylation mapping of canine cMyBP-C using IMAC and MS/MS identified five phosphorylation sites, including three novel sites. In order to further evaluate this finding in a different model, cMyBP-C phosphorylation was examined in a rat model of global stunning. In the rat model, stunning was associated with increased phosphorylation of cMyBP-C at a critical calcium/calmodulin-dependent kinase II site, and the increased phosphorylation was largely inhibited when stunning was prevented by either ischemic preconditioning or reperfusion in the presence of low-calcium buffer. These data indicate cMyBP-C phosphorylation plays an important role in myocardial stunning.

Original languageEnglish (US)
Pages (from-to)4176-4186
Number of pages11
JournalProteomics
Volume6
Issue number14
DOIs
StatePublished - Jul 1 2006

Keywords

  • Difference gel electrophoresis
  • Myocardial stunning
  • Myosin binding protein C
  • Phosphorylation
  • Tandem mass spectrometry

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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