ArticleJournal of molecular and cellular cardiology2019
Ablation of the calpain-targeted site in cardiac myosin binding protein-C is cardioprotective during ischemia-reperfusion injury.
Article in Journal of molecular and cellular cardiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Fast skeletal myosin binding protein-C expression exacerbates dysfunction in heart failure.Basic research in cardiology · 2026Article
- Proteolytic degradation of atrial sarcomere proteins underlies contractile defects in atrial fibrillation.American journal of physiology. Heart and circulatory physiology · 2024Article
- Roles of cMyBP-C phosphorylation on cardiac contractile dysfunction inJournal of molecular and cellular cardiology plus · 2024Article
- Hypertrophic cardiomyopathy inThe journal of cardiovascular aging · 2024Article
- Myosin-binding protein H-like regulates myosin-binding protein distribution and function in atrial cardiomyocytes.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Calpain and Cardiometabolic Diseases.International journal of molecular sciences · 2023Review
- The roles of intracellular proteolysis in cardiac ischemia-reperfusion injury.Basic research in cardiology · 2023Review
- Myofilament Alterations Associated with Human R14del-Phospholamban Cardiomyopathy.International journal of molecular sciences · 2023Article
- Mechano-growth factor E-domain modulates cardiac contractile function through 14-3-3 protein interactomes.Frontiers in physiology · 2022Article
- Amino terminus of cardiac myosin binding protein-C regulates cardiac contractility.Journal of molecular and cellular cardiology · 2021Article
- Targeted inhibition of calpain in mitochondria alleviates oxidative stress-induced myocardial injury.Acta pharmacologica Sinica · 2021Article
- Creating a 'Molecular Band-Aid'; Blocking an Exposed Protease Target Site in Desmoplakin.Journal of personalized medicine · 2021Article
- Upregulation of transient receptor potential melastatin 4 (TRPM4) in ventricular fibroblasts from heart failure patients.Pflugers Archiv : European journal of physiology · 2021Article
- NHJournal of cellular signaling · 2021Article
- Calpain activation mediates microgravity-induced myocardial abnormalities in mice via p38 and ERK1/2 MAPK pathways.The Journal of biological chemistry · 2020Article
- Under construction: The dynamic assembly, maintenance, and degradation of the cardiac sarcomere.Journal of molecular and cellular cardiology · 2020Review
- Phosphorylation of cardiac myosin-binding protein-C contributes to calcium homeostasis.The Journal of biological chemistry · 2020Article
- Genetic, clinical, molecular, and pathogenic aspects of the South Asian-specific polymorphic MYBPC3Biophysical reviews · 2020Review
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Authors and funding
20 authors at 13 institutions in 5 countries.
Funding
Abstract
Cardiac myosin binding protein-C (cMyBP-C) phosphorylation is essential for normal heart function and protects the heart from ischemia-reperfusion (I/R) injury. It is known that protein kinase-A (PKA)-mediated phosphorylation of cMyBP-C prevents I/R-dependent proteolysis, whereas dephosphorylation of cMyBP-C at PKA sites correlates with its degradation. While sites on cMyBP-C associated with phosphorylation and proteolysis co-localize, the mechanisms that link cMyBP-C phosphorylation and proteolysis during cardioprotection are not well understood. Therefore, we aimed to determine if abrogation of cMyBP-C proteolysis in association with calpain, a calcium-activated protease, confers cardioprotection during I/R injury. Calpain is activated in both human ischemic heart samples and ischemic mouse myocardium where cMyBP-C is dephosphorylated and undergoes proteolysis. Moreover, cMyBP-C is a substrate for calpain proteolysis and cleaved by calpain at residues 272-TSLAGAGRR-280, a domain termed as the calpain-target site (CTS). Cardiac-specific transgenic (Tg) mice in which the CTS motif was ablated were bred into a cMyBP-C null background. These Tg mice were conclusively shown to possess a normal basal structure and function by analysis of histology, electron microscopy, immunofluorescence microscopy, Q-space MRI of tissue architecture, echocardiography, and hemodynamics. However, the genetic ablation of the CTS motif conferred resistance to calpain-mediated proteolysis of cMyBP-C. Following I/R injury, the loss of the CTS reduced infarct size compared to non-transgenic controls. Collectively, these findings demonstrate the physiological significance of calpain-targeted cMyBP-C proteolysis and provide a rationale for studying inhibition of calpain-mediated proteolysis of cMyBP-C as a therapeutic target for cardioprotection.
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