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Exercise-induced peptide TAG-23 protects cardiomyocytes from reperfusion injury through regulating PKG–cCbl interaction
- Source :
- Basic Research in Cardiology
- Publication Year :
- 2021
- Publisher :
- Springer Berlin Heidelberg, 2021.
-
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. Supplementary Information The online version contains supplementary material available at 10.1007/s00395-021-00878-4.
- Subjects :
- Physiology
Caspase 3
Peptide
Apoptosis
medicine.disease_cause
Ubiquitin
cCbl
Physiology (medical)
medicine
Humans
Myocytes, Cardiac
Viability assay
TAG-23
chemistry.chemical_classification
biology
PKG
Original Contribution
medicine.disease
Cell biology
Ubiquitin ligase
Myocardial infarction
Oxidative Stress
chemistry
Doxorubicin
Reperfusion Injury
biology.protein
Cardiology and Cardiovascular Medicine
Peptides
Reperfusion injury
Oxidative stress
Subjects
Details
- Language :
- English
- ISSN :
- 14351803 and 03008428
- Volume :
- 116
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Basic Research in Cardiology
- Accession number :
- edsair.doi.dedup.....9d5aa338d639054d1a8db3dfb6dd8572