Tanshinone IIA Inhibits β-Catenin Nuclear Translocation and IGF-2R Activation via Estrogen Receptors to Suppress Angiotensin II-Induced H9c2 Cardiomyoblast Cell Apoptosis
Autor: | Peramaiyan Rajendran, Cecilia Hsuan Day, Jaw Ji Yang, Vijaya Padma Viswanadha, Nien Hung Lee, Yu Feng Chen, Chih Hsueh Lin, Ya Fang Chen, Chih Yang Huang, Ray Jade Chen |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
medicine.medical_specialty β-Catenin Estrogen receptor Apoptosis Salvia miltiorrhiza Inflammation Estrogen receptors H9c2 Cardiomyoblasts Receptor IGF Type 2 Cell Line Muscle hypertrophy 03 medical and health sciences Internal medicine medicine Animals Humans Myocytes Cardiac Phosphorylation Receptor beta Catenin Cell Nucleus Insulin-like Growth Factor-2 Receptor Chemistry Angiotensin II Tanshinone IIA General Medicine Cardiomyopathy Hypertrophic Rats Cell biology Protein Transport 030104 developmental biology Endocrinology Receptors Estrogen Catenin Abietanes cardiovascular system medicine.symptom Research Paper Drugs Chinese Herbal Signal Transduction |
Zdroj: | International Journal of Medical Sciences |
ISSN: | 1449-1907 |
Popis: | 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. |
Databáze: | OpenAIRE |
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