14 December 2017
Int J Med Sci 2017; 14(12):1284-1291. doi:10.7150/ijms.20396
Tanshinone IIA Inhibits β-Catenin Nuclear Translocation and IGF-2R Activation via Estrogen Receptors to Suppress Angiotensin II-Induced H9c2 Cardiomyoblast Cell Apoptosis
1. Graduate Institute of Basic Medical Science, China Medical University, Taichung 40402, Taiwan;
Cardiomyopathy involves changes in the myocardial ultra-structure, hypertrophy, apoptosis, fibrosis and inflammation. Angiotensin II (AngII) stimulates the expression of insulin like-growth factors (IGF-2) and IGF-2 receptor (IGF-2R) in H9c2 cardiomyoblasts and subsequently leads to apoptosis. Estrogen receptors protect cardiomyocytes from apoptosis and fibrosis. Tanshinone IIA (TSN), a main active ingredient from Danshen, has been shown to protect cardiomyocytes from death caused by different stress signals. Estrogen receptor α (ER) is required for the rapid activation of the IGF-1R signaling cascade. This study aimed to investigate whether TSN protected H9c2 cardiomyocytes from AngII-induced activation of IGF-2R pathway and hypertrophy via ERs. We found that AngII caused the reduction in IGF-1R phosphorylation and the elevation of β-catenin and IGF-2R levels. This was reversed by increasing doses of TSN and of caspase-3 and ERK1/2 phosphorylation mediated by ERs. The phytoestrogen significantly attenuated AngII-induced apoptosis and suppressed the subsequent cardiac remodeling effect. Therefore, TSN reduced the AngII-induced activation of β-catenin and IGF-2R pathways, apoptosis and cardiac remodeling via ERs in H9c2 cardiomyoblasts.
Keywords: Angiotensin II, β-Catenin, Estrogen receptors, H9c2 Cardiomyoblasts, Insulin-like Growth Factor-2 Receptor, Tanshinone IIA.
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How to cite this article:
Chen YF, Day CH, Lee NH, Chen YF, Yang JJ, Lin CH, Chen RJ, Rajendran P, Viswanadha VP, Huang CY. Tanshinone IIA Inhibits β-Catenin Nuclear Translocation and IGF-2R Activation via Estrogen Receptors to Suppress Angiotensin II-Induced H9c2 Cardiomyoblast Cell Apoptosis. Int J Med Sci 2017; 14(12):1284-1291. doi:10.7150/ijms.20396. Available from http://www.medsci.org/v14p1284.htm