O-linked GlcNAc modification of cardiac myofilament proteins: a novel regulator of myocardial contractile function.
Circ Res
; 103(12): 1354-8, 2008 Dec 05.
Article
em En
| MEDLINE
| ID: mdl-18988896
ABSTRACT
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Acetilglucosamina
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Citoesqueleto de Actina
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Contração Miocárdica
/
Miocárdio
Limite:
Animals
Idioma:
En
Revista:
Circ Res
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos