Exercise-induced peptide TAG-23 protects cardiomyocytes from reperfusion injury through regulating PKG-cCbl interaction.
Basic Res Cardiol
; 116(1): 41, 2021 06 25.
Article
em En
| MEDLINE
| ID: mdl-34173041
ABSTRACT
Recent studies have revealed that proper exercise can reduce the risk of chronic disease and is beneficial to the body. Peptides have been shown to play an important role in various pathological processes, including cardiovascular diseases. However, little is known about the role of exercise-induced peptides in cardiovascular disease. We aimed to explore the function and mechanism of TAG-23 peptide in reperfusion injury and oxidative stress. Treatment with TAG-23 peptide significantly improved cell viability, the mitochondrial membrane potential, and ROS levels and reduced LDH release, the apoptosis rate and caspase 3 activation in vitro. In vivo, TAG-23 ameliorated MI and heart failure induced by I/R or DOX treatment. Pull-down assays showed that TAG-23 can bind to PKG . The TAG-23-PKG complex inhibited PKG degradation through the UPS. We also identified cCbl as the E3 ligase of PKG and found that the interaction between these proteins was impaired by TAG-23 treatment. In addition, we provided evidence that TAG-23 mediated Lys48-linked polyubiquitination and subsequent proteasomal degradation. Our results reveal that a novel exercise-induced peptide, TAG-23, can inhibit PKG degradation by serving as a competitive binding peptide to attenuate the formation of the PKG-cCbl complex. Treatment with TAG-23 may be a new therapeutic approach for reperfusion injury.
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Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão
/
Miócitos Cardíacos
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article