title: Ferrous Iron Induces Nrf2 Expression in Mouse Brain Astrocytes to Prevent Neurotoxicity.
abstract: 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.
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Zhenwen
authors.initials: Z
authors.lastname: Cui
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Baofeng
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Yuhao
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.|Department of Neurosurgery, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Qingfang
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.|Neuroscience and Neuroengineering Research Center, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, China.
authors.forename: Guo-Yuan
authors.initials: GY
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. sjturj10086@yahoo.com.
authors.forename: Liuguan
authors.initials: L
authors.lastname: Bian
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005296:Ferrous Compounds / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D005296:Ferrous Compounds; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D007770:L-Lactate Dehydrogenase; C029451:ferrous chloride
keywords: Astrocyte; Fe2+; Neurotoxicity; Nrf2; Oxidative Stress