Cardiac ischemic preconditioning promotes cMyBP-C phosphorylation by inhibiting the calpain-mediated proteolysis.
Exp Cell Res
; 433(2): 113859, 2023 12 15.
Article
em En
| MEDLINE
| ID: mdl-38000772
ABSTRACT
Ischemic preconditioning (IPC) has been considered as the most important mean to protect against ischemia/reperfusion (I/R) induced heart injury. It has been reported that cardiac myosin binding protein-C (cMyBP-C) phosphorylation plays an essential role in cardiac protection against I/R-induced heart injury. However, it is still obscured whether IPC-mediated cardiac protection is causally related to cMyBP-C phosphorylation and proteolysis and, if so, what the underlying mechanism is. In this study, IPC was found to increase the phosphorylation level of cMyBP-C, companying with the decreased calpain activity in the collected perfusate samples. Mechanistically, we confirmed that IPC promoted cMyBP-C phosphorylation and inhibited calpain-mediated cMyBP-C proteolysis. Moreover, inhibition of calpain activity significantly increased the phosphorylated cMyBP-C level by using calpain inhibitor (MG-101), and subsequently promoted stabilization and secretion of cMyBP-C. Functionally, adeno-associated virus (AAV)-mediated overexpression of mutated phosphorylation motif site of cMyBP-C exhibited impaired IPC-mediated cardiac protection via proteolysis of the full-length cMyBP-C protein. We concluded that IPC promoted cMyBP-C phosphorylation via inhibition of calpain-mediated proteolysis and participated in IPC-mediated protection against I/R induced heart injury.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão
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Precondicionamento Isquêmico
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Traumatismos Cardíacos
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article