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miR-494 Contributes to Estrogen Protection of Cardiomyocytes Against Oxidative Stress via Targeting (NF-κB) Repressing Factor

Oxidative stress plays a pivotal role in the initiation and progression of cardiac diseases. Estrogens have been demonstrated to exert pleiotropic cardioprotective effects, among which antioxidative stress is one of the key effects linking estrogens to cardioprotection. By using a microRNAs (miRs) m...

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Autores principales: Tang, Zhi-Ping, Zhao, Wei, Du, Jian-kui, Ni, Xin, Zhu, Xiao-Yan, Lu, Jian-Qiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5960695/
https://www.ncbi.nlm.nih.gov/pubmed/29867756
http://dx.doi.org/10.3389/fendo.2018.00215
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author Tang, Zhi-Ping
Zhao, Wei
Du, Jian-kui
Ni, Xin
Zhu, Xiao-Yan
Lu, Jian-Qiang
author_facet Tang, Zhi-Ping
Zhao, Wei
Du, Jian-kui
Ni, Xin
Zhu, Xiao-Yan
Lu, Jian-Qiang
author_sort Tang, Zhi-Ping
collection PubMed
description Oxidative stress plays a pivotal role in the initiation and progression of cardiac diseases. Estrogens have been demonstrated to exert pleiotropic cardioprotective effects, among which antioxidative stress is one of the key effects linking estrogens to cardioprotection. By using a microRNAs (miRs) microarray screening approach, we discovered an increase in miR-494, which is known to exert cardioprotective effects, in estrogen-treated cardiomyocytes. We hypothesized that the upregulation of miR-494 might contribute to estrogen-mediated cardioprotection against oxidative stress. We found that E(2) stimulates miR-494 expression via ERα in both cardiomyocytes and the myocardium of female mice. The miR-494 inhibitor attenuated the protective effect of 17β-estradiol (E(2)) against oxidative stress-induced injury in cardiomyocytes. By contrast, the miR-494 mimic protected cardiomyocytes against oxidative stress-induced cardiomyocyte injury. Using real-time PCR, western blot and dual-luciferase reporter gene analyses, we identified nuclear factor kappa B (NF-κB) repressing factor (NKRF) as the miR-494 target in cardiomyocytes. E(2) was found to inhibit NKRF, thus activating NF-κB through a miR-494-dependent mechanism. In addition, the protective effects of E(2) and miR-494 against oxidative stress in cardiomyocytes were eliminated by the NF-κB inhibitor. In summary, this study demonstrates for the first time that estrogen inhibits NKRF expression through ERα-mediated upregulation of miR-494 in cardiomyocytes, leading to the activation of NF-κB, which in turn results in an increase in antioxidative defense. ERα-mediated upregulation of miR-494 may contribute to estrogen protection of cardiomyocytes against oxidative stress.
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spelling pubmed-59606952018-06-04 miR-494 Contributes to Estrogen Protection of Cardiomyocytes Against Oxidative Stress via Targeting (NF-κB) Repressing Factor Tang, Zhi-Ping Zhao, Wei Du, Jian-kui Ni, Xin Zhu, Xiao-Yan Lu, Jian-Qiang Front Endocrinol (Lausanne) Endocrinology Oxidative stress plays a pivotal role in the initiation and progression of cardiac diseases. Estrogens have been demonstrated to exert pleiotropic cardioprotective effects, among which antioxidative stress is one of the key effects linking estrogens to cardioprotection. By using a microRNAs (miRs) microarray screening approach, we discovered an increase in miR-494, which is known to exert cardioprotective effects, in estrogen-treated cardiomyocytes. We hypothesized that the upregulation of miR-494 might contribute to estrogen-mediated cardioprotection against oxidative stress. We found that E(2) stimulates miR-494 expression via ERα in both cardiomyocytes and the myocardium of female mice. The miR-494 inhibitor attenuated the protective effect of 17β-estradiol (E(2)) against oxidative stress-induced injury in cardiomyocytes. By contrast, the miR-494 mimic protected cardiomyocytes against oxidative stress-induced cardiomyocyte injury. Using real-time PCR, western blot and dual-luciferase reporter gene analyses, we identified nuclear factor kappa B (NF-κB) repressing factor (NKRF) as the miR-494 target in cardiomyocytes. E(2) was found to inhibit NKRF, thus activating NF-κB through a miR-494-dependent mechanism. In addition, the protective effects of E(2) and miR-494 against oxidative stress in cardiomyocytes were eliminated by the NF-κB inhibitor. In summary, this study demonstrates for the first time that estrogen inhibits NKRF expression through ERα-mediated upregulation of miR-494 in cardiomyocytes, leading to the activation of NF-κB, which in turn results in an increase in antioxidative defense. ERα-mediated upregulation of miR-494 may contribute to estrogen protection of cardiomyocytes against oxidative stress. Frontiers Media S.A. 2018-05-14 /pmc/articles/PMC5960695/ /pubmed/29867756 http://dx.doi.org/10.3389/fendo.2018.00215 Text en Copyright © 2018 Tang, Zhao, Du, Ni, Zhu and Lu. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Tang, Zhi-Ping
Zhao, Wei
Du, Jian-kui
Ni, Xin
Zhu, Xiao-Yan
Lu, Jian-Qiang
miR-494 Contributes to Estrogen Protection of Cardiomyocytes Against Oxidative Stress via Targeting (NF-κB) Repressing Factor
title miR-494 Contributes to Estrogen Protection of Cardiomyocytes Against Oxidative Stress via Targeting (NF-κB) Repressing Factor
title_full miR-494 Contributes to Estrogen Protection of Cardiomyocytes Against Oxidative Stress via Targeting (NF-κB) Repressing Factor
title_fullStr miR-494 Contributes to Estrogen Protection of Cardiomyocytes Against Oxidative Stress via Targeting (NF-κB) Repressing Factor
title_full_unstemmed miR-494 Contributes to Estrogen Protection of Cardiomyocytes Against Oxidative Stress via Targeting (NF-κB) Repressing Factor
title_short miR-494 Contributes to Estrogen Protection of Cardiomyocytes Against Oxidative Stress via Targeting (NF-κB) Repressing Factor
title_sort mir-494 contributes to estrogen protection of cardiomyocytes against oxidative stress via targeting (nf-κb) repressing factor
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5960695/
https://www.ncbi.nlm.nih.gov/pubmed/29867756
http://dx.doi.org/10.3389/fendo.2018.00215
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