Dataset Information

MiR-494 Contributes to Estrogen Protection of Cardiomyocytes Against Oxidative Stress via Targeting (NF-?B) Repressing Factor.

ABSTRACT: 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 ER? in both cardiomyocytes and the myocardium of female mice. The miR-494 inhibitor attenuated the protective effect of 17?-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-?B) repressing factor (NKRF) as the miR-494 target in cardiomyocytes. E2 was found to inhibit NKRF, thus activating NF-?B 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-?B inhibitor. In summary, this study demonstrates for the first time that estrogen inhibits NKRF expression through ER?-mediated upregulation of miR-494 in cardiomyocytes, leading to the activation of NF-?B, which in turn results in an increase in antioxidative defense. ER?-mediated upregulation of miR-494 may contribute to estrogen protection of cardiomyocytes against oxidative stress.

SUBMITTER: Tang ZP

PROVIDER: S-EPMC5960695 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

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

Tang Zhi-Ping ZP Zhao Wei W Du Jian-Kui JK Ni Xin X Zhu Xiao-Yan XY Lu Jian-Qiang JQ

Frontiers in endocrinology 20180514

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-4 ...[more]

PMID: 29867756

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Project description:Muscles of sarcopenic people show hypotrophic myofibers and infiltration with adipose and, at later stages, fibrotic tissue. The origin of infiltrating adipocytes resides in fibro-adipogenic precursors and nonmyogenic mesenchymal progenitor cells, and in satellite cells, the adult stem cells of skeletal muscles. Myoblasts and brown adipocytes share a common Myf5+ progenitor cell: the cell fate depends on levels of bone morphogenetic protein 7 (BMP-7), a TGF-β family member. S100B, a Ca2+-binding protein of the EF-hand type, is expressed at relatively high levels in myoblasts from sarcopenic humans and exerts anti-myogenic effects via NF-κB-dependent inhibition of MyoD, a myogenic transcription factor acting upstream of the essential myogenic factor, myogenin. Adipogenesis requires high levels of ROS, and myoblasts of sarcopenic subjects show elevated ROS levels. Here we show that: (1) ROS overproduction in myoblasts results in upregulation of S100B levels via NF-κB activation; and (2) ROS/NF-κB-induced accumulation of S100B causes myoblast transition into brown adipocytes. S100B activates an NF-κB/Ying Yang 1 axis that negatively regulates the promyogenic and anti-adipogenic miR-133 with resultant accumulation of the brown adipogenic transcription regulator, PRDM-16. S100B also upregulates BMP-7 via NF-κB/Ying Yang 1 with resultant BMP-7 autocrine activity. Interestingly, myoblasts from sarcopenic humans show features of brown adipocytes. We also show that S100B levels and NF-κB activity are elevated in brown adipocytes obtained by culturing myoblasts in adipocyte differentiation medium and that S100B knockdown or NF-κB inhibition in myoblast-derived brown adipocytes reconverts them into fusion-competent myoblasts. At last, interstitial cells and, unexpectedly, a subpopulation of myofibers in muscles of geriatric but not young mice co-express S100B and the brown adipocyte marker, uncoupling protein-1. These results suggest that S100B is an important intracellular molecular signal regulating Myf5+ progenitor cell differentiation into fusion-competent myoblasts or brown adipocytes depending on its levels.

Dataset Information

MiR-494 Contributes to Estrogen Protection of Cardiomyocytes Against Oxidative Stress via Targeting (NF-?B) Repressing Factor.

Publications

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

Similar Datasets

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