Activation of Nrf2 by MIND4-17 protects osteoblasts from hydrogen peroxide-induced oxidative stress

MIND4-17 is a recently developed NF-E2-related factor 2 (Nrf2) activator, which uniquely causes Nrf2 disassociation from Keap1. Here, we showed that pretreatment with MIND4-17 significantly inhibited hydrogen peroxide (H O )-induced viability reduction of primary osteoblasts and OB-6 osteoblastic ce...

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Published in:Oncotarget 2017-12, Vol.8 (62), p.105662-105672
Main Authors: Guo, Shiguang, Fei, Hao-Dong, Ji, Feng, Chen, Feng-Li, Xie, Yue, Wang, Shou-Guo
Format: Article
Language:English
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Research Paper
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Summary:MIND4-17 is a recently developed NF-E2-related factor 2 (Nrf2) activator, which uniquely causes Nrf2 disassociation from Keap1. Here, we showed that pretreatment with MIND4-17 significantly inhibited hydrogen peroxide (H O )-induced viability reduction of primary osteoblasts and OB-6 osteoblastic cells. Meanwhile, MIND4-17 inhibited both apoptotic and non-apoptotic osteoblast cell death by H O . MIND4-17 treatment induced Keap1-Nrf2 disassociation, causing Nrf2 stabilization, accumulation and nuclear translocation in osteoblasts, leading to transcription of several Nrf2-dependent genes, including and . Additionally, MIND4-17 largely attenuated H O -reactive oxygen species (ROS) production, lipid peroxidation and DNA damages. Nrf2 knockdown by targeted short hairpin RNA (shRNA) exacerbated H O -induced cytotoxicity in OB-6 osteoblastic cells, and nullified MIND4-17-mediated cytoprotection against H O . Meanwhile, Keap1 shRNA took over MIND4-17's actions and protected OB-6 cells from H O . Together, MIND4-17 activates Nrf2 signaling and protects osteoblasts from H O .
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.22360