Nitrosylation of β2-Tubulin Promotes Microtubule Disassembly and Differentiated Cardiomyocyte Beating in Ischemic Mice

Da Hyeon Choi, Seong Ki Kang, Kyeong Eun Lee, Jongsun Jung, Eun Ju Kim, Won Ho Kim, Young Guen Kwon, Kwang Pyo Kim, Inho Jo, Yoon Shin Park, Sang Ick Park

Research output: Contribution to journalArticlepeer-review


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 β2-tubulin (Y106 and Y340) underwent nitrosylation (Tyr-NO) by endogenously generated NO during cardiomyocyte differentiation from pre-cardiomyocyte-like P19CL6 cells. Results:: Tyr-NO-β2-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-β2-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, β2-tubulin, that can promote normal cardiac beating and cardiomyocyte regeneration. Taken together, we suggest therapeutic potential of Tyr-NO-β2-tubulin, for ischemic cardiomyocyte, which can reduce unexpected side effect of stem cell transplantation, arrhythmogenesis.

Original languageEnglish
Pages (from-to)921-937
Number of pages17
JournalTissue Engineering and Regenerative Medicine
Issue number6
StatePublished - Oct 2023

Bibliographical note

Publisher Copyright:
© 2023, Korean Tissue Engineering and Regenerative Medicine Society.


  • Cardiomyogenesis
  • Microtubule-Stathmin
  • Nitric oxide
  • Tyrosine nitrosylation
  • eNOS


Dive into the research topics of 'Nitrosylation of β2-Tubulin Promotes Microtubule Disassembly and Differentiated Cardiomyocyte Beating in Ischemic Mice'. Together they form a unique fingerprint.

Cite this