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Ferrous Iron Induces Nrf2 Expression in Mouse Brain Astrocytes to Prevent Neurotoxicity
Author(s) -
Cui Zhenwen,
Zhong Zhihong,
Yang Yong,
Wang Baofeng,
Sun Yuhao,
Sun Qingfang,
Yang Guoyuan,
Bian Liuguan
Publication year - 2016
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.21803
Subject(s) - neurotoxicity , cytotoxicity , astrocyte , ferrous , chemistry , microbiology and biotechnology , pharmacology , oxidative stress , toxicity , biology , biochemistry , in vitro , neuroscience , central nervous system , organic chemistry
Free radical damage caused by ferrous iron is involved in the pathogenesis of secondary brain injury after intracerebral hemorrhage (ICH). NF‐E2‐related factor 2 (Nrf2), a major phase II gene regulator that binds to antioxidant response element, represents an important cellular cytoprotective mechanism against oxidative damage. We hypothesized that Nrf2 might protect astrocytes from damage by Fe 2+ . Therefore, we examined cytotoxicity in primary astrocytes induced by iron overload and evaluated the effects of Fe 2+ on Nrf2 expression. The results demonstrated that 24‐h Fe 2+ exposure exerted time‐ and concentration‐dependent cytotoxicity in astrocytes. Furthermore, Fe 2+ exposure in astrocytes resulted in time‐ and concentration‐dependent increases in Nrf2 expression, which preceded Fe 2+ toxicity. Nrf2‐specific siRNA further knocked down Nrf2 levels, resulting in greater Fe 2+ ‐induced astrocyte cytotoxicity. These data indicate that induction of Nrf2 expression could serve as an adaptive self‐defense mechanism, although it is insufficient to completely protect primary astrocytes from Fe 2+ ‐induced neurotoxicity.