title: Involvement of NF-kappaB and AP-1 activation in icariin promoted cardiac differentiation of mouse embryonic stem cells.
abstract: Icariin has been reported to facilitate the differentiation of mouse embryonic stem (ES) cells into cardiomyocytes; however, the mechanism on cardiomyogenic cell lineage differentiation has not been fully elucidated yet. In the present studies, an underlying signaling network including p38, extracellular signal-regulated kinase 1, 2 (ERK1, 2), nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1) transcription factors c-jun and c-fos was assumed in icariin induced cardiomyogenesis. Icariin rapidly activated p38 and ERK1, 2 in embryoid bodies, treatment with p38 antagonist 4-(4-Fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole (SB203580) or ERK1, 2 inhibitor 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene (U0126) significantly abolished icariin induced cardiac commitment, MEF2C gene expression and nuclear translocation, as well as cardiac-specific protein alpha-actinin expression, indicating that p38 and ERK1, 2 are specifically involved in icariin stimulated cardiomyogenic cell lineage differentiation of ES cells. Further, IkappaBalpha phosphorylation and NF-kappaB p65 translocation to the nucleus appeared rapidly when embryoid bodies exposed to icariin, and the expression of IkappaBalpha or NF-kappaB p65 in cytoplasm was decreased concomitantly. Moreover, icariin increased c-jun and c-fos mRNA and protein expression. Either SB203580 or U0126 displayed inhibitory effect on icariin induced NF-kappaB and AP-1 activation. It could be concluded that p38 and ERK1, 2 are activated in a coordinated manner, which in turn contribute to NF-kappaB and AP-1 activation in icariin induced cardiomyogenic cell lineage differentiation of mouse ES cells.
authors.affiliation: Department of Cardio-Cerebral Vascular and Hepatic Pharmacology, Institute of Pharmacology & Toxicology and Biochemical Pharmaceutics, Zhejiang University, Hangzhou 310058, China.
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Wo
authors.forename: Danyan
authors.initials: D
authors.lastname: Zhu
authors.forename: Yongping
authors.initials: Y
authors.lastname: Yu
authors.forename: Yijia
authors.initials: Y
authors.lastname: Lou
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D019070:Cell Lineage / Q000502:physiology; D053595:Embryonic Stem Cells / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007930:Leucine / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009206:Myocardium / Q000166:cytology*; D016328:NF-kappa B / Q000502:physiology*; D016759:Oncogene Protein p65(gag-jun) / Q000502:physiology; D016761:Oncogene Proteins v-fos / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000502:physiology*
chemical_list: D005419:Flavonoids; D016328:NF-kappa B; D016759:Oncogene Protein p65(gag-jun); D016761:Oncogene Proteins v-fos; D018808:Transcription Factor AP-1; D020928:Mitogen-Activated Protein Kinases; D007930:Leucine; C056599:icariin