Tanshinone IIA Prevents Leu27IGF-II-Induced Cardiomyocyte Hypertrophy Mediated by Estrogen Receptor and Subsequent Akt Activation

doi:10.1142/S0192415X15500895

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Title:	Tanshinone IIA Prevents Leu27IGF-II-Induced Cardiomyocyte Hypertrophy Mediated by Estrogen Receptor and Subsequent Akt Activation
Authors:	Weng, Yueh-Shan Wang, Hsueh-Fang Pai, Pei-Ying Jong, Gwo-Ping Lai, Chao-Hung Chung, Li-Chin Hsieh, Dennis Jine-Yuan HsuanDay, Cecilia Kuo, Wei-Wen Huang, Chih-Yang
Contributors:	醫務管理系(所)
Keywords:	Tanshinone IIA Selective Estrogen Receptor Modulator IGF-II Receptor Cardiac Hypertrophy Calcineurin/NFAT3 p-akt
Date:	2015
Issue Date:	2016-04-19 19:00:12 (UTC+8)
Publisher:	World Scientific Publ Co Pte Ltd
Abstract:	IGF-IIR plays important roles as a key regulator in myocardial pathological hypertrophy and apoptosis, which subsequently lead to heart failure. Salvia miltiorrhiza Bunge (Danshen) is a traditional Chinese medicinal herb used to treat cardiovascular diseases. Tanshinone IIA is an active compound in Danshen and is structurally similar to 17 beta-estradiol (E-2). However, whether tanshinone IIA improves cardiomyocyte survival in pathological hypertrophy through estrogen receptor (ER) regulation remains unclear. This study investigates the role of ER signaling in mediating the protective effects of tanshinone IIA on IGF-IIR-induced myocardial hypertrophy. Leu27IGF-II (IGF-II analog) was shown in this study to specifically activate IGF-IIR expression and ICI 182,780 (ICI), an ER antagonist used to investigate tanshinone IIA estrogenic activity. We demonstrated that tanshinone IIA significantly enhanced Akt phosphorylation through ER activation to inhibit Leu27IGF-II-induced calcineurin expression and subsequent NFATc3 nuclear translocation to suppress myocardial hypertrophy. Tanshinone IIA reduced the cell size and suppressed ANP and BNP, inhibiting antihypertrophic effects induced by Leu27IGF-II. The cardioprotective properties of tanshinone IIA that inhibit Leu27IGF-II-induced cell hypertrophy and promote cell survival were reversed by ICI. Furthermore, ICI significantly reduced phospho-Akt, Ly294002 (PI3K inhibitor), and PI3K siRNA significantly reduced the tanshinone IIA-induced protective effect. The above results suggest that tanshinone IIA inhibited cardiomyocyte hypertrophy, which was mediated through ER, by activating the PI3K/Akt pathway and inhibiting Leu27IGF-II-induced calcineurin and NFATC3. Tanshinone IIA exerted strong estrogenic activity and therefore represented a novel selective ER modulator that inhibits IGF-IIR signaling to block cardiac hypertrophy.
Relation:	American Journal of Chinese Medicine, v.43 n.8, pp.1567-1591
Appears in Collections:	[Dept. of Hospital and Health (including master's program)] Periodical Articles

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