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Myosin binding protein C is differentially phosphorylated upon myocardial stunning in canine and rat hearts — Evidence for novel phosphorylation sites
Author(s) -
Yuan Chao,
Guo Yurong,
Ravi Rajashree,
Przyklenk Karin,
Shilkofski Nicole,
Diez Roberto,
Cole Robert N.,
Murphy Anne M.
Publication year - 2006
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200500894
Subject(s) - phosphorylation , stunning , myocardial stunning , protein phosphorylation , phosphoprotein , myosin light chain kinase , calmodulin , biology , myofilament , myosin , microbiology and biotechnology , ischemia , medicine , calcium , protein kinase a
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.