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Aim: To investigate the effect of icariin on the expression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1alpha), peroxisome proliferator-activated receptor alpha (PPARalpha), 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 alpha-actinin, troponin T) were evaluated when embryoid bodies (EB) were treated with icariin or retinoid acid. The expression of PGC-1alpha, PPARalpha, 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 alpha-actinin and troponin T. The expression of PGC-1alpha, PPARalpha, 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-1alpha, PPARalpha, 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-1alpha, PPARalpha, and NRF-1.

Conclusion: Taken together, icariin promoted the expression of PGC-1alpha, PPARalpha, 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.

Titel:	Icariin promotes expression of PGC-1alpha, PPARalpha, and NRF-1 during cardiomyocyte differentiation of murine embryonic stem cells in vitro.
Autor/in / Beteiligte Person:	Ding, L ; Liang, XG ; Zhu, DY ; Lou, YJ
Link:	Zum Volltext
Zeitschrift:	Acta pharmacologica Sinica, Jg. 28 (2007-10-01), Heft 10, S. 1541
Veröffentlichung:	2009- : New York : Nature Publishing Group ; <i>Original Publication</i>: Beijing, China : Science Press, c2000-, 2007
Medientyp:	academicJournal
ISSN:	1671-4083 (print)
DOI:	10.1111/j.1745-7254.2007.00648.x
Schlagwort:	Animals Blotting, Western Dose-Response Relationship, Drug Embryonic Stem Cells metabolism Enzyme Inhibitors pharmacology Epimedium chemistry Flavonoids administration & dosage Flavonoids isolation & purification Imidazoles pharmacology Mice Myocytes, Cardiac metabolism Nuclear Respiratory Factor 1 biosynthesis Nuclear Respiratory Factor 1 genetics PPAR alpha biosynthesis PPAR alpha genetics Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Phosphorylation drug effects Plants, Medicinal chemistry Pyridines pharmacology RNA, Messenger biosynthesis RNA, Messenger genetics Reverse Transcriptase Polymerase Chain Reaction Trans-Activators biosynthesis Trans-Activators genetics Transcription Factors genetics p38 Mitogen-Activated Protein Kinases metabolism Cell Differentiation drug effects Embryonic Stem Cells cytology Flavonoids pharmacology Myocytes, Cardiac cytology Transcription Factors biosynthesis
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Acta Pharmacol Sin] 2007 Oct; Vol. 28 (10), pp. 1541-9. MeSH Terms: Cell Differentiation / drug effects ; Embryonic Stem Cells / cytology ; Flavonoids / pharmacology ; Myocytes, Cardiac / cytology ; Transcription Factors / *biosynthesis ; Animals ; Blotting, Western ; Dose-Response Relationship, Drug ; Embryonic Stem Cells / metabolism ; Enzyme Inhibitors / pharmacology ; Epimedium / chemistry ; Flavonoids / administration & dosage ; Flavonoids / isolation & purification ; Imidazoles / pharmacology ; Mice ; Myocytes, Cardiac / metabolism ; Nuclear Respiratory Factor 1 / biosynthesis ; Nuclear Respiratory Factor 1 / genetics ; PPAR alpha / biosynthesis ; PPAR alpha / genetics ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Phosphorylation / drug effects ; Plants, Medicinal / chemistry ; Pyridines / pharmacology ; RNA, Messenger / biosynthesis ; RNA, Messenger / genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Trans-Activators / biosynthesis ; Trans-Activators / genetics ; Transcription Factors / genetics ; p38 Mitogen-Activated Protein Kinases / metabolism Substance Nomenclature: 0 (Enzyme Inhibitors) ; 0 (Flavonoids) ; 0 (Imidazoles) ; 0 (Nrf1 protein, mouse) ; 0 (Nuclear Respiratory Factor 1) ; 0 (PPAR alpha) ; 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha) ; 0 (Ppargc1a protein, mouse) ; 0 (Pyridines) ; 0 (RNA, Messenger) ; 0 (Trans-Activators) ; 0 (Transcription Factors) ; EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) ; OU13V1EYWQ (SB 203580) ; VNM47R2QSQ (icariin) Entry Date(s): Date Created: 20070922 Date Completed: 20081118 Latest Revision: 20161124 Update Code: 20231215

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Icariin promotes expression of PGC-1alpha, PPARalpha, and NRF-1 during cardiomyocyte differentiation of murine embryonic stem cells in vitro.