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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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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. |
format | Online Article Text |
id | pubmed-5580914 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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