Journal
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
Volume 14, Issue 12, Pages 1284-1291Publisher
IVYSPRING INT PUBL
DOI: 10.7150/ijms.20396
Keywords
Angiotensin II; beta-Catenin; Estrogen receptors; H9c2 Cardiomyoblasts; Insulin-like Growth Factor-2 Receptor; Tanshinone IIA
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Funding
- Taiwan Ministry of Health and Welfare Clinical Trial
- Research Center of Excellence [MOHW106-TDU-B-212-113004]
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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 a (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 beta-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 beta-catenin and IGF-2R pathways, apoptosis and cardiac remodeling via ERs in H9c2 cardiomyoblasts.
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