Icariin-mediated expression of cardiac genes and modulation of nitric oxide signaling pathway during differentiation of mouse embryonic stem cells into cardiomyocytes in vitro
Icariin-mediated expression of cardiac genes and modulation of nitric oxide signaling pathway during differentiation of mouse embryonic stem cells into cardiomyocytes in vitro作者机构：Department of Pharmacology and Toxicology College of Pharmaceutical Sciences Zhejiang University Hangzhou China
出 版 物：《Acta Pharmacologica Sinica》 (中国药理学报(英文版))
年 卷 期：2006年第27卷第3期
页 面：311-320页
核心收录：
学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学]
基 金：Project supported by the National Natural Sciences Foundation of China(№30171121) the Key Grant of the Chinese Ministry of Education(№03088) the International Joint Key Grant of Zhejiang Province(No 2003C24005)
主 题：embryonic stem cells cardiomyocytes icariin cardiac-specific genes cAMP cGMP nitric oxide
摘 要：Aim:To investigate effects of icariin on cardiac gene expression and the modula-tion of nitric oxide(NO)signal transduction during the differentiation of embry-onic stem(ES)cells into cardiomyocytes in ***:The expression levelsof cardiac developmental-dependent genes were measured using reverse tran-scription-polymerase chain reaction(RT-PCR).The chronotropic responses ofcardiomyocytes to β-adrenoceptor stimulation were *** levels ofcAMP and cGMP in ES cells were measured using ***-enous NO levels were measured by using the Griess ***(AG)was used to confirm the influence of icariin on the endogenous NO ***:Icariin significantly elevated mRNA levels of cardiac tran-scription factors GATA4 and Nkx2.5,and cardiac-specific α-MHC,MLC-2v and β-AR genes in a concentration-and time-dependent manner(P0.05).Cardiomyo-cytes derived from embryoid body(EB)treated with icariin were more sensitive toisoprenaline(P0.01).Treatment of ES cells with icariin resulted in a continuedelevation in the cAMP/cGMP ratio before a shift to the cardiomyocyte phenotype(P0.05).AG decreased the NO level,and delayed and decreased the incidence ofcontracting EB to only approximately 35% on d 5+11,an effect that could berescued by *** cells were cocultured with icariin and AG,the percentageof beating EB reached a peak level of 73% on d 5+11(P0.05),Conclusion:Theinducible effects of icariin were partly related to increase in the expression ofcardiac developmental-dependent genes,and elevation of the cAMP/cGMP ratioin ES cells,as well as upregulation of endogenous NO generation during the earlystages of cardiac development.
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