Abstract
Aim:
To investigate the effect of icariin on the expression of peroxisome proliferator-activated receptor γ coactivator-1 alpha (PGC-1α), peroxisome proliferator-activated receptor alpha (PPARα), and nuclear respiratory factor 1 (NRF-1) on cardiomyocyte differentiation of murine embryonic stem (ES) cells in vitro.
Methods:
The cardiomyocytes derived from murine ES cells were verified by immunocytochemistry using confocal laser scanning microscopy. Cardiac-specific sarcomeric proteins (ie α-actinin, troponin T) were evaluated when embryoid bodies (EB) were treated with icariin or retinoid acid. The expression of PGC-1α, PPARα, and NRF-1 were analyzed using both semiquantitative RT-PCR and Western blotting in cardiomyocyte differentiation. The phosphorylation of the p38 mitogen-activated protein kinase (MAPK) was studied in the differentiation process, and its specific inhibitor SB203580 was employed to confirm the function of the p38 MAPK on icariin-induced cardiac differentiation.
Results:
The application of icariin significantly induced the cardiomyocyte differentiation of EB as indicated by the promoted expression of α-actinin and troponin T. The expression of PGC-1α, PPARα, and NRF-1 increased coincidently in early differentiation and the increase was dose-dependently upregulated by icariin treatment. The phosphorylation of the p38 MAPK peaked on d 6 and decreased after d 8, and the activation was further enhanced and prolonged when the EB were subjected to icariin, which was concurrent with the elevation of PGC-1α, PPARα, and NRF-1. Moreover, the inhibition of the p38 MAPK pathway by SB203580 efficiently abolished icariin-stimulated cardiomyocyte differentiation and resulted in the capture of the upregulation of PGC-1α, PPARα, and NRF-1.
Conclusion:
Taken together, icariin promoted the expression of PGC-1α, PPARα, and NRF-1 during cardiomyocyte differentiation of murine ES cells in vitro and the effect was partly responsible for the activation of the p38 MAPK.
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This project was supported by the National Natural Sciences Foundation of China (No 30171121, 30472112, and 30672564), the Key Grant of the Chinese Ministry of Education (No 03088), and the International Joint Key Grant of Zhejiang Province (No 2003C24005).
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Ding, L., Liang, Xg., Zhu, Dy. et al. Icariin promotes expression of PGC-1α, PPARα, and NRF-1 during cardiomyocyte differentiation of murine embryonic stem cells in vitro. Acta Pharmacol Sin 28, 1541–1549 (2007). https://doi.org/10.1111/j.1745-7254.2007.00648.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00648.x
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