Tissue Eng Regen Med.
2023 Oct;20(6):921-937. 10.1007/s13770-023-00582-5.
Nitrosylation of b2-Tubulin Promotes Microtubule Disassembly and Differentiated Cardiomyocyte Beating in Ischemic Mice
- Affiliations
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- 1Department of Biological Sciences and Biotechnology, School of Biological Sciences, College of Natural Sciences, Chungbuk National University, Cheongju, Republic of Korea
- 2Division of Intractable Diseases, Center for Biomedical Sciences, Korea National Institute of Health (KNIH), Cheongju, Republic of Korea
- 3Department of Applied Chemistry, Kyung Hee University, Yongin, Republic of Korea
- 4Division of Cardiovascular and Rare Diseases, Center for Biomedical Sciences, Korea National Institute of Health, Cheongju, Republic of Korea
- 5Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea
- 6Department of Molecular Medicine, College of Ewha Womans University, Seoul, Republic of Korea
- 7Graduate Program in System Health Science and Engineering, Ewha Womans University, Seoul, Republic of Korea
- 8Department of Laboratory Medicine, Green Cross Laboratories, Yongin, Republic of Korea
- 9AI Drug Platform Center, Syntekabio, Daejeon, Republic of Korea
- KMID: 2546841
- DOI: http://doi.org/10.1007/s13770-023-00582-5
Abstract
- BACKGROUND
Beating cardiomyocyte regeneration therapies have revealed as alternative therapeutics for heart transplantation. Nonetheless, the importance of nitric oxide (NO) in cardiomyocyte regeneration has been widely suggested, little has been reported concerning endogenous NO during cardiomyocyte differentiation.
METHODS
Here, we used P19CL6 cells and a Myocardiac infarction (MI) model to confirm NO-induced protein modification and its role in cardiac beating. Two tyrosine (Tyr) residues of b2-tubulin (Y106 and Y340) underwent nitrosylation (Tyr-NO) by endogenously generated NO during cardiomyocyte differentiation from pre-cardiomyocyte-like P19CL6 cells.
RESULTS
Tyr-NO-b2-tubulin mediated the interaction with Stathmin, which promotes microtubule disassembly, and was prominently observed in spontaneously beating cell clusters and mouse embryonic heart (E11.5d). In myocardial infarction mice, Tyr-NO-b2-tubulin in transplanted cells was closely related with cardiac troponin-T expression with their functional recovery, reduced infarct size and thickened left ventricular wall.
CONCLUSION
This is the first discovery of a new target molecule of NO, b2-tubulin, that can promote normal cardiac beating and cardiomyocyte regeneration. Taken together, we suggest therapeutic potential of Tyr-NO-b2-tubulin, for ischemic cardiomyocyte, which can reduce unexpected side effect of stem cell transplantation, arrhythmogenesis.
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