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E2/ER β inhibit ISO-induced cardiac cellular hypertrophy by suppressing Ca(2+)-calcineurin signaling

Cardiovascular incidences are markedly higher in men than in pre-menstrual women. However, this advantage in women declines with aging and therefore can be correlated with the sex hormone 17β-Estradiol (E2) which is reported to protect heart cells by acting though estrogen receptors (ERs). In this s...

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Autores principales: Tsai, Cheng-Yen, Kuo, Wei-Wen, Shibu, Marthandam Asokan, Lin, Yueh-Min, Liu, Chien-Nam, Chen, Yi-Hui, Day, Cecilia-Hsuan, Shen, Chia-Yao, Viswanadha, Vijaya Padma, Huang, Chih-Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5580914/
https://www.ncbi.nlm.nih.gov/pubmed/28863192
http://dx.doi.org/10.1371/journal.pone.0184153
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author Tsai, Cheng-Yen
Kuo, Wei-Wen
Shibu, Marthandam Asokan
Lin, Yueh-Min
Liu, Chien-Nam
Chen, Yi-Hui
Day, Cecilia-Hsuan
Shen, Chia-Yao
Viswanadha, Vijaya Padma
Huang, Chih-Yang
author_facet Tsai, Cheng-Yen
Kuo, Wei-Wen
Shibu, Marthandam Asokan
Lin, Yueh-Min
Liu, Chien-Nam
Chen, Yi-Hui
Day, Cecilia-Hsuan
Shen, Chia-Yao
Viswanadha, Vijaya Padma
Huang, Chih-Yang
author_sort Tsai, Cheng-Yen
collection PubMed
description Cardiovascular incidences are markedly higher in men than in pre-menstrual women. However, this advantage in women declines with aging and therefore can be correlated with the sex hormone 17β-Estradiol (E2) which is reported to protect heart cells by acting though estrogen receptors (ERs). In this study we have determined the effect of E2/ERβ against ISO induced cellular hypertrophy in H9c2 cardiomyoblast cells. The results confirm that ISO induced cardiac-hypertrophy by elevating the levels of hypertrophy associated proteins, ANP and BNP and further by upregulating p-CaMKII, calcineurin, p-GATA4 and NFATc3 which was correlated with a significant enlargement of the H9c2 cardiomyoblast. However, overexpression of ERβ and/or administration of E2 inhibited ISO-induced hypertrophy in H9c2 cells. In addition, E2/ERβ also inhibited ISO-induced NFATc3 translocation, and reduced the protein level of downstream marker, BNP. Furthermore, by testing with the calcineurin inhibitor (CsA), it was confirmed that calcineurin acted as a key mediator for the anti-hypertrophic effect of E2/ERβ. In cells treated with calcium blocker (BATPA), the inhibitory effect of E2/ERβ on ISO-induced Ca(2+) influx and hypertrophic effects were totally blocked suggesting that E2/ERβ inhibited calcineurin activity to activate I-1 protein and suppress PP1, then induce PLB protein phosphorylation and activation, resulting in Ca(2+) reuptake into sarcoplasmic reticulum through SR Ca(2+) cycling modification. In conclusion, E2/ERβ suppresses the Ca(2+) influx and calcineurin activity induced by ISO to enhance the PLB protein activity and SR Ca(2+) cycling.
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spelling pubmed-55809142017-09-15 E2/ER β inhibit ISO-induced cardiac cellular hypertrophy by suppressing Ca(2+)-calcineurin signaling Tsai, Cheng-Yen Kuo, Wei-Wen Shibu, Marthandam Asokan Lin, Yueh-Min Liu, Chien-Nam Chen, Yi-Hui Day, Cecilia-Hsuan Shen, Chia-Yao Viswanadha, Vijaya Padma Huang, Chih-Yang PLoS One Research Article Cardiovascular incidences are markedly higher in men than in pre-menstrual women. However, this advantage in women declines with aging and therefore can be correlated with the sex hormone 17β-Estradiol (E2) which is reported to protect heart cells by acting though estrogen receptors (ERs). In this study we have determined the effect of E2/ERβ against ISO induced cellular hypertrophy in H9c2 cardiomyoblast cells. The results confirm that ISO induced cardiac-hypertrophy by elevating the levels of hypertrophy associated proteins, ANP and BNP and further by upregulating p-CaMKII, calcineurin, p-GATA4 and NFATc3 which was correlated with a significant enlargement of the H9c2 cardiomyoblast. However, overexpression of ERβ and/or administration of E2 inhibited ISO-induced hypertrophy in H9c2 cells. In addition, E2/ERβ also inhibited ISO-induced NFATc3 translocation, and reduced the protein level of downstream marker, BNP. Furthermore, by testing with the calcineurin inhibitor (CsA), it was confirmed that calcineurin acted as a key mediator for the anti-hypertrophic effect of E2/ERβ. In cells treated with calcium blocker (BATPA), the inhibitory effect of E2/ERβ on ISO-induced Ca(2+) influx and hypertrophic effects were totally blocked suggesting that E2/ERβ inhibited calcineurin activity to activate I-1 protein and suppress PP1, then induce PLB protein phosphorylation and activation, resulting in Ca(2+) reuptake into sarcoplasmic reticulum through SR Ca(2+) cycling modification. In conclusion, E2/ERβ suppresses the Ca(2+) influx and calcineurin activity induced by ISO to enhance the PLB protein activity and SR Ca(2+) cycling. Public Library of Science 2017-09-01 /pmc/articles/PMC5580914/ /pubmed/28863192 http://dx.doi.org/10.1371/journal.pone.0184153 Text en © 2017 Tsai et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Tsai, Cheng-Yen
Kuo, Wei-Wen
Shibu, Marthandam Asokan
Lin, Yueh-Min
Liu, Chien-Nam
Chen, Yi-Hui
Day, Cecilia-Hsuan
Shen, Chia-Yao
Viswanadha, Vijaya Padma
Huang, Chih-Yang
E2/ER β inhibit ISO-induced cardiac cellular hypertrophy by suppressing Ca(2+)-calcineurin signaling
title E2/ER β inhibit ISO-induced cardiac cellular hypertrophy by suppressing Ca(2+)-calcineurin signaling
title_full E2/ER β inhibit ISO-induced cardiac cellular hypertrophy by suppressing Ca(2+)-calcineurin signaling
title_fullStr E2/ER β inhibit ISO-induced cardiac cellular hypertrophy by suppressing Ca(2+)-calcineurin signaling
title_full_unstemmed E2/ER β inhibit ISO-induced cardiac cellular hypertrophy by suppressing Ca(2+)-calcineurin signaling
title_short E2/ER β inhibit ISO-induced cardiac cellular hypertrophy by suppressing Ca(2+)-calcineurin signaling
title_sort e2/er β inhibit iso-induced cardiac cellular hypertrophy by suppressing ca(2+)-calcineurin signaling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5580914/
https://www.ncbi.nlm.nih.gov/pubmed/28863192
http://dx.doi.org/10.1371/journal.pone.0184153
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