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microRNA-455 targets cullin 3 to activate Nrf2 signaling and protect human osteoblasts from hydrogen peroxide
Over-production of hydrogen peroxide (H(2)O(2)) will lead to human osteoblast dysfunction and apoptosis, causing progression of osteoporosis and osteonecrosis. NF-E2-related factor 2 (Nrf2) is a well-characterized anti-oxidant signaling. Cullin 3 (Cul3) ubiquitin E3 ligase dictates Nrf2 degradation....
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601727/ https://www.ncbi.nlm.nih.gov/pubmed/28938631 http://dx.doi.org/10.18632/oncotarget.19486 |
Sumario: | Over-production of hydrogen peroxide (H(2)O(2)) will lead to human osteoblast dysfunction and apoptosis, causing progression of osteoporosis and osteonecrosis. NF-E2-related factor 2 (Nrf2) is a well-characterized anti-oxidant signaling. Cullin 3 (Cul3) ubiquitin E3 ligase dictates Nrf2 degradation. We demonstrate that microRNA-455 (“miR-455”) is a putative Cul3-targeting microRNA. Forced-expression of miR-455 in both hFOB1. 19 osteoblast cell line and primary human osteoblasts induced Cul3 degradation and Nrf2 protein stabilization, which led to subsequent transcription of ARE (anti-oxidant response element)-dependent genes (NQO1, HO1 and GCLC). Cul3 silencing, by expressing miR-455 or targeted-shRNA, protected human osteoblasts from H(2)O(2). Reversely, miR-455 anti-sense caused Cul3 accumulation and Nrf2 degradation, which exacerbated H(2)O(2) damages in hFOB1. 19 cells. Moreover, forced over-expression of Cul3 in hFOB1. 19 cells silenced Nrf2 and sensitized H(2)O(2). Together, we propose that miR-455 activated Nrf2 signaling and protected human osteoblasts from oxidative stress possibly via targeting Cul3. |
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