Tanshinone-induced ERs suppresses IGFII activation to alleviate Ang II-mediated cardiac hypertrophy |
| |
Authors: | Ya-Fang Chen Nien-Hung Lee Pei-Ying Pai Li-Chin Chung Chia-Yao Shen Peramaiyan Rajendran |
| |
Affiliation: | 1. Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan;2. Department of Obstetrics and Gynecology, Taichung Veteran’s General Hospital, Taichung, Taiwan;3. Division of Cardiology, China Medical University Hospital, Taichung, Taiwan;4. Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy &5. Science, Tainan County, Taiwan;6. Department of Nursing, MeiHo University, Pingtung, Taiwan |
| |
Abstract: | Cardiomyopathy involves changes in myocardial ultrastructure and cardiac hypertrophy. Angiotensin II (AngII) has previously been shown to stimulate the expression of IGF-2 and IGF-2R in H9c2 cardiomyoblasts and increase of blood pressure, and cardiac hypertrophy. Estrogen receptors (ERs) exert protective effects, such as anti-hypertrophy in cadiomyocytes. Tanshinone IIA (TSN), a main active ingredient from a Chinese medical herb, Salvia miltiorrhiza Bunge (Danshen), was shown to protect cardiomyocytes hypertrophy by different stress signals. We aimed to investigate whether TSN protected H9c2 cardiomyocytes from AngII-induced activation of IGF-2R pathway and hypertrophy by mediating through ERs. AngII resulted in H9c2 cardiomyoblast hypertrophy and increased inflammatory molecular markers. These were down-regulated by TSN via estrogen receptors. AngII resulted in elevation in MAPKs, IGF-2R and hypertrophic protein markers. These, again, were reduced by addition of the phytoestrogen with activation of ERs. Finally, AngII induced phosphorylation of heat shock factor-1 (HSF1) and decreased sirtuin-1 (SIRT1). In addition, AngII also caused an increase in distribution of IGF-2R molecules on cell membrane. In contrast, TSN reduced HSF1 phosphorylation and cell surface IGF-2R while elevating SIRT1 via ERs. TSN was capable of attenuating AngII-induced IGF-2R pathway and hypertrophy through ERs in H9c2 cardiomyoblast cells. |
| |
Keywords: | Angiotensin II estrogen receptors H9c2 cardiomyoblasts hypertrophy IGF-2R tanshinone IIA |
|
|