E2/ER β enhances calcineurin protein degradation and PI3k/Akt/MDM2 signal transduction to inhibit ISO-induced myocardial cell apoptosis

Kuan Ho Lin, Wei Wen Kuo, Marthandam Asokan Shibu, Cecilia Hsuan Day, You Liang Hsieh, Li Chin Chung, Ray Jade Chen, Su Ying Wen, Vijaya Padma Viswanadha, Chih Yang Huang

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Secretion of multifunctional estrogen and its receptor has been widely considered as the reason for markedly higher frequency of heart disease in men than in women. 17β-Estradiol (E2), for instance, has been reported to prevent development of cardiac apoptosis via activation of estrogen receptors (ERs). In addition, protein phosphatase such as protein phosphatase 1 (PP1) and calcineurin (PP2B) are also involved in cardiac hypertrophy and cell apoptosis signaling. However, the mechanism by which E2/ERβ suppresses apoptosis is not fully understood, and the role of protein phosphatase in E2/ERβ action also needs further investigation. In this study, we observed that E2/ERβ inhibited isoproterenol (ISO)-induced myocardial cell apoptosis, cytochrome c release and downstream apoptotic markers. Moreover, we found that E2/ERβ blocks ISO-induced apoptosis in H9c2 cells through the enhancement of calcineurin protein degradation through PI3K/Akt/MDM2 signaling pathway. Our results suggest that supplementation with estrogen and/or overexpression of estrogen receptor β gene may prove to be effective means to treat stress-induced myocardial damage.

Original languageEnglish
Article number892
JournalInternational Journal of Molecular Sciences
Volume18
Issue number4
DOIs
Publication statusPublished - Apr 24 2017

Fingerprint

estrogens
Signal transduction
Calcineurin
apoptosis
Cell death
Isoproterenol
Estrogen Receptors
Proteolysis
Signal Transduction
Apoptosis
degradation
proteins
Proteins
Degradation
cells
phosphatases
Phosphatases
Phosphoprotein Phosphatases
Protein Phosphatase 1
heart diseases

Keywords

  • 17β-Estradiol
  • Apoptosis
  • Calcineurin
  • Cardiac apoptosis
  • Isoproterenol

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Computer Science Applications
  • Spectroscopy
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

E2/ER β enhances calcineurin protein degradation and PI3k/Akt/MDM2 signal transduction to inhibit ISO-induced myocardial cell apoptosis. / Lin, Kuan Ho; Kuo, Wei Wen; Shibu, Marthandam Asokan; Day, Cecilia Hsuan; Hsieh, You Liang; Chung, Li Chin; Chen, Ray Jade; Wen, Su Ying; Viswanadha, Vijaya Padma; Huang, Chih Yang.

In: International Journal of Molecular Sciences, Vol. 18, No. 4, 892, 24.04.2017.

Research output: Contribution to journalArticle

Lin, Kuan Ho ; Kuo, Wei Wen ; Shibu, Marthandam Asokan ; Day, Cecilia Hsuan ; Hsieh, You Liang ; Chung, Li Chin ; Chen, Ray Jade ; Wen, Su Ying ; Viswanadha, Vijaya Padma ; Huang, Chih Yang. / E2/ER β enhances calcineurin protein degradation and PI3k/Akt/MDM2 signal transduction to inhibit ISO-induced myocardial cell apoptosis. In: International Journal of Molecular Sciences. 2017 ; Vol. 18, No. 4.
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