Tanshinone-induced ERs suppresses IGFII activation to alleviate Ang II-mediated cardiac hypertrophy

J Recept Signal Transduct Res. 2017 Oct;37(5):493-499. doi: 10.1080/10799893.2017.1360349.

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; H9c2 cardiomyoblasts; IGF-2R; estrogen receptors; hypertrophy; tanshinone IIA.

MeSH terms

  • Abietanes / administration & dosage*
  • Angiotensin II / administration & dosage
  • Angiotensin II / metabolism
  • Animals
  • Cardiomegaly / drug therapy*
  • Cardiomegaly / genetics
  • Cardiomegaly / pathology
  • Cell Line
  • Drugs, Chinese Herbal / administration & dosage
  • Gene Expression / drug effects
  • Heat Shock Transcription Factors / genetics
  • Humans
  • Insulin-Like Growth Factor II / genetics*
  • Insulin-Like Growth Factor II / metabolism
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Rats
  • Receptor, IGF Type 2 / genetics*
  • Receptor, IGF Type 2 / metabolism
  • Receptors, Estrogen / genetics
  • Signal Transduction / drug effects
  • Sirtuin 1 / genetics

Substances

  • Abietanes
  • Drugs, Chinese Herbal
  • Heat Shock Transcription Factors
  • Hsf1 protein, rat
  • Receptor, IGF Type 2
  • Receptors, Estrogen
  • tanshinone
  • Angiotensin II
  • Insulin-Like Growth Factor II
  • Mitogen-Activated Protein Kinase Kinases
  • Sirt1 protein, rat
  • Sirtuin 1