Abstract | BACKGROUND: In mammals, regenerative therapy after myocardial infarction is hampered by the limited regenerative capacity of adult heart, whereas a transient regenerative capacity is maintained in the neonatal heart. Systemic phosphorylation signaling analysis on ischemic neonatal myocardium might be helpful to identify key pathways involved in heart regeneration. Our aim was to define the kinase-substrate network in ischemic neonatal myocardium and to identify key pathways involved in heart regeneration after ischemic insult. METHODS: Quantitative phosphoproteomics profiling was performed on infarct border zone of neonatal myocardium, and kinase-substrate network analysis revealed 11 kinases with enriched substrates and upregulated phosphorylation levels, including checkpoint kinase 1 ( CHK1) kinase. The effect of CHK1 on cardiac regeneration was tested on Institute of Cancer Research CD1 neonatal and adult mice that underwent apical resection or myocardial infarction. RESULTS: CONCLUSIONS: Our study indicates that phosphoproteome of neonatal regenerative myocardium could help identify important signaling pathways involved in myocardial regeneration. CHK1 is found to be a key signaling responsible for neonatal regeneration. Myocardial overexpression of CHK1 could improve cardiac regeneration in adult hearts by activating the mammalian target of rapamycin C1/ ribosomal protein S6 kinase b-1 pathway. Thus, CHK1 might serve as a potential novel target in myocardial repair after myocardial infarction.
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Authors | Yi Fan, Yiwei Cheng, Yafei Li, Bingrui Chen, Zimu Wang, Tianwen Wei, Hao Zhang, Yueshuai Guo, Qiming Wang, Yongyue Wei, Feng Chen, Jiahao Sha, Xuejiang Guo, Liansheng Wang |
Journal | Circulation
(Circulation)
Vol. 141
Issue 19
Pg. 1554-1569
(05 12 2020)
ISSN: 1524-4539 [Electronic] United States |
PMID | 32098494
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Proteome
- Checkpoint Kinase 1
- Chek1 protein, mouse
- Mechanistic Target of Rapamycin Complex 1
- Ribosomal Protein S6 Kinases, 70-kDa
- ribosomal protein S6 kinase, 70kD, polypeptide 1
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Topics |
- Age Factors
- Animals
- Animals, Newborn
- Cell Proliferation
- Cells, Cultured
- Checkpoint Kinase 1
(genetics, metabolism)
- Disease Models, Animal
- Mechanistic Target of Rapamycin Complex 1
(metabolism)
- Mice, Inbred ICR
- Myocardial Infarction
(enzymology, pathology, physiopathology)
- Myocardium
(enzymology, metabolism)
- Phosphorylation
- Proteome
- Regeneration
- Ribosomal Protein S6 Kinases, 70-kDa
(metabolism)
- Signal Transduction
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