Tanshinone IIA inhibits β-catenin nuclear translocation and IGF-2R activation via estrogen receptors to suppress angiotensin II-induced H9c2 cardiomyoblast cell apoptosis

Ya Fang Chen, Cecilia Hsuan Day, Nien Hung Lee, Yu Feng Chen, Jaw Ji Yang, Chih Hsueh Lin, Ray Jade Chen, Peramaiyan Rajendran, Vijaya Padma Viswanadha, Chih Yang Huang

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1284-1291
Number of pages8
JournalInternational Journal of Medical Sciences
Volume14
Issue number12
DOIs
Publication statusPublished - Sep 30 2017

Keywords

  • Angiotensin II
  • Estrogen receptors
  • H9c2 cardiomyoblasts
  • Insulin-like growth factor-2 receptor
  • Tanshinone IIA
  • β-catenin

ASJC Scopus subject areas

  • Medicine(all)

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