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

Author:

Weng Yueh-Shan1,Wang Hsueh-Fang2,Pai Pei-Ying3,Jong Gwo-Ping4,Lai Chao-Hung54,Chung Li-Chin6,Hsieh Dennis Jine-Yuan7,HsuanDay Cecilia8,Kuo Wei-Wen9,Huang Chih-Yang11011

Affiliation:

1. Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan

2. Institute of Biomedical Nutrition, Hungkuang University, Taichung, Taiwan

3. Division of Cardiology, China Medical University Hospital, Taichung, Taiwan

4. Division of Cardiology, Armed Force Taichung General Hospital, Taichung, Taiwan

5. Graduate Institute of Aging Medicine, China Medical University, Taichung, Taiwan

6. Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy & Science, Tainan County, Taiwan

7. School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan

8. Department of Nursing, Mei Ho University, Pingguang Road, Pingtung, Taiwan

9. Department of Biological Science and Technology, China Medical University, Taichung, Taiwan

10. Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan

11. Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan

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[Formula: see text]-estradiol (E[Formula: see text]. 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.

Publisher

World Scientific Pub Co Pte Lt

Subject

Complementary and alternative medicine,General Medicine

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