17β-Estradiol and/or estrogen receptor alpha signaling blocks protein phosphatase 1 mediated ISO induced cardiac hypertrophy

Hsin-Yuan Fang, Meng Yu Hung, Yueh Min Lin, Sudhir Pandey, Chia Chien Chang, Kuan Ho Lin, Chia Yao Shen, Vijaya Padma Viswanadha, Wei Wen Kuo, Chih-Yang Huang

Research output: Contribution to journalArticle

Abstract

Earlier studies have shown that estrogen possess protective function against the development of pathological cardiac hypertrophy. However, the molecular mechanisms of estrogens (E2) protective effect are poorly understood. Additionally, abnormal activation of β-adrenergic signaling have been implicated in the development of pathological cardiac remodeling. However, the role of serine/threonine protein phosphatase 1 (PP1) in pathological cardiac remodeling under the influence of β-adrenergic signaling have been sparsely investigated. In this study, we assessed the downstream effects of abnormal activation of PP1 upon isoproterenol (ISO) induced pathological cardiac changes. We found that pre-treatment of 17β-estradiol (E2), tet-on estrogen receptor-α, or both significantly inhibited ISO-induced increase in cell size, hypertrophy marker gene expression and cytosolic calcium accumulation in H9c2 cells. Additionally, treatment with estrogen receptor inhibitor (ICI) reversed those effects, implicating role of E2 in inhibiting pathological cardiac remodeling. However, specific inhibition of ERα using melatonin, reduced ISO-induced PP1c expression and enhanced the level of ser-16 phosphorylated phospholamban (PLB), responsible for regulation of sarcoplasmic reticulum Ca2+-ATPase (SERCA) activity. Furthermore, hypertrophic effect caused by overexpression of PP1cα was reduced by treatment with specific inhibitor of ERα. Collectively, we found that estrogen and estrogen receptor-α have protective effect against pathological cardiac changes by suppressing PP1 expression and its downstream signaling pathway, which further needs to be elucidated.

LanguageEnglish (US)
Article numbere0196569
JournalPloS one
Volume13
Issue number5
DOIs
StatePublished - May 1 2018

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Protein Phosphatase 1
phosphoprotein phosphatase
Estrogen Receptor alpha
Cardiomegaly
hypertrophy
Isoproterenol
estradiol
Estrogens
estrogens
Adrenergic Agents
Chemical activation
protective effect
Calcium-Transporting ATPases
Sarcoplasmic Reticulum
Melatonin
Threonine
Cell Size
Gene expression
Estrogen Receptors
Serine

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

17β-Estradiol and/or estrogen receptor alpha signaling blocks protein phosphatase 1 mediated ISO induced cardiac hypertrophy. / Fang, Hsin-Yuan; Hung, Meng Yu; Lin, Yueh Min; Pandey, Sudhir; Chang, Chia Chien; Lin, Kuan Ho; Shen, Chia Yao; Viswanadha, Vijaya Padma; Kuo, Wei Wen; Huang, Chih-Yang.

In: PloS one, Vol. 13, No. 5, e0196569, 01.05.2018.

Research output: Contribution to journalArticle

Fang, Hsin-Yuan ; Hung, Meng Yu ; Lin, Yueh Min ; Pandey, Sudhir ; Chang, Chia Chien ; Lin, Kuan Ho ; Shen, Chia Yao ; Viswanadha, Vijaya Padma ; Kuo, Wei Wen ; Huang, Chih-Yang. / 17β-Estradiol and/or estrogen receptor alpha signaling blocks protein phosphatase 1 mediated ISO induced cardiac hypertrophy. In: PloS one. 2018 ; Vol. 13, No. 5.
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