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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-05-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fendo.2018.00215/full |
| _version_ | 1818055033694978048 |
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| author | Zhi-Ping Tang Zhi-Ping Tang Zhi-Ping Tang Wei Zhao Jian-kui Du Xin Ni Xiao-Yan Zhu Jian-Qiang Lu |
| author_facet | Zhi-Ping Tang Zhi-Ping Tang Zhi-Ping Tang Wei Zhao Jian-kui Du Xin Ni Xiao-Yan Zhu Jian-Qiang Lu |
| author_sort | Zhi-Ping Tang |
| collection | DOAJ |
| 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 E2 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 (E2) 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. E2 was found to inhibit NKRF, thus activating NF-κB through a miR-494-dependent mechanism. In addition, the protective effects of E2 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. |
| first_indexed | 2024-12-10T12:06:31Z |
| format | Article |
| id | doaj.art-28e38d7af3784b8b94d87d75544057ae |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-10T12:06:31Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-28e38d7af3784b8b94d87d75544057ae2022-12-22T01:49:27ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922018-05-01910.3389/fendo.2018.00215326719miR-494 Contributes to Estrogen Protection of Cardiomyocytes Against Oxidative Stress via Targeting (NF-κB) Repressing FactorZhi-Ping Tang0Zhi-Ping Tang1Zhi-Ping Tang2Wei Zhao3Jian-kui Du4Xin Ni5Xiao-Yan Zhu6Jian-Qiang Lu7The Key Laboratory of Exercise and Health Sciences of Ministry of Education, School of Kinesiology, Shanghai University of Sport, Shanghai, ChinaDepartment of Physiology, Second Military Medical University, Shanghai, ChinaResearch Laboratory of Burn and Trauma, PLA 181 Hospital, Guilin, ChinaDepartment of Physiology, Second Military Medical University, Shanghai, ChinaDepartment of Physiology, Second Military Medical University, Shanghai, ChinaDepartment of Physiology, Second Military Medical University, Shanghai, ChinaDepartment of Physiology, Second Military Medical University, Shanghai, ChinaThe Key Laboratory of Exercise and Health Sciences of Ministry of Education, School of Kinesiology, Shanghai University of Sport, Shanghai, ChinaOxidative 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 E2 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 (E2) 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. E2 was found to inhibit NKRF, thus activating NF-κB through a miR-494-dependent mechanism. In addition, the protective effects of E2 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.http://journal.frontiersin.org/article/10.3389/fendo.2018.00215/fullmiR-494estrogencardiomyocytesoxidative stress(NF-κB) repressing factor |
| spellingShingle | Zhi-Ping Tang Zhi-Ping Tang Zhi-Ping Tang Wei Zhao Jian-kui Du Xin Ni Xiao-Yan Zhu Jian-Qiang Lu miR-494 Contributes to Estrogen Protection of Cardiomyocytes Against Oxidative Stress via Targeting (NF-κB) Repressing Factor Frontiers in Endocrinology miR-494 estrogen cardiomyocytes oxidative stress (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 | miR-494 estrogen cardiomyocytes oxidative stress (NF-κB) repressing factor |
| url | http://journal.frontiersin.org/article/10.3389/fendo.2018.00215/full |
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