E2/ER β inhibit ISO-induced cardiac cellular hypertrophy by suppressing Ca<superscript>2+</superscript>-calcineurin signaling.
In: PLoS ONE, Jg. 12 (2017-09-01), Heft 9, S. 1-15
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Zugriff:
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. [ABSTRACT FROM AUTHOR]
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E2/ER β inhibit ISO-induced cardiac cellular hypertrophy by suppressing Ca<superscript>2+</superscript>-calcineurin signaling.
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Autor/in / Beteiligte Person: | 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 |
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Zeitschrift: | PLoS ONE, Jg. 12 (2017-09-01), Heft 9, S. 1-15 |
Veröffentlichung: | 2017 |
Medientyp: | academicJournal |
ISSN: | 1932-6203 (print) |
DOI: | 10.1371/journal.pone.0184153 |
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