Iron accentuated reactive oxygen species release by NADPH oxidase in activated microglia contributes to oxidative stress in vitro 11 Medical and Health Sciences 1109 Neurosciences
JournalJournal of Neuroinflammation
PublisherBioMed Central Ltd.
MetadataShow full item record
AbstractBackground: Excessive iron contributes to oxidative stress after central nervous system injury. NADPH oxidase (NOX) enzymes are upregulated in microglia after pro-inflammatory activation and contribute to oxidative stress. The relationship between iron, microglia, NOX, and oxidative stress is currently unclear. Methods: We evaluated the effects of iron on lipopolysaccharide (LPS)-activated microglia and its secondary effect within neuronal co-cultures. Further, NOX2 and four specific inhibitors were tested to evaluate the relationship with the reactive oxygen species (ROS)-producing enzymes. Results: An iron dose-dependent increase in ROS production among microglia treated with LPS was identified. Interestingly, despite this increase in ROS, inflammatory polarization alterations were not detected among the microglia after exposure to iron and LPS. Co-culture experimentation between primary neurons and exposed microglia (iron and LPS) significantly reduced neuronal cell number at 24 h, suggesting a profound neurotoxic effect despite the lack of a change in polarization phenotype. NOX2 and NOX4 inhibition significantly reduced ROS production among microglia exposed to iron and LPS and reduced neuronal damage and death in response to microglial co-culture. Conclusions: In conclusion, iron significantly increased ROS production and neurotoxicity without exacerbating LP-activated microglia phenotype in vitro, suggesting that iron contributes to microglia-related oxidative stress, and this may be a viable therapeutic target for injury or neurodegeneration. Further, this study highlights both NOX2 and NOX4 as potential therapeutic targets in the treatment of iron-induced microglia-related inflammation and neurotoxicity. Copyright 2019 The Author(s).
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85061845566&doi=10.1186%2fs12974-019-1430-7&partnerID=40&md5=cb292293ac319f10378e367860195191; http://hdl.handle.net/10713/8597
- NADPH oxidase and aging drive microglial activation, oxidative stress, and dopaminergic neurodegeneration following systemic LPS administration.
- Authors: Qin L, Liu Y, Hong JS, Crews FT
- Issue date: 2013 Jun
- Paeonol attenuates microglia-mediated inflammation and oxidative stress-induced neurotoxicity in rat primary microglia and cortical neurons.
- Authors: Tseng YT, Hsu YY, Shih YT, Lo YC
- Issue date: 2012 Mar
- Interactive role of the toll-like receptor 4 and reactive oxygen species in LPS-induced microglia activation.
- Authors: Qin L, Li G, Qian X, Liu Y, Wu X, Liu B, Hong JS, Block ML
- Issue date: 2005 Oct
- Apocyanin, a Microglial NADPH Oxidase Inhibitor Prevents Dopaminergic Neuronal Degeneration in Lipopolysaccharide-Induced Parkinson's Disease Model.
- Authors: Sharma N, Nehru B
- Issue date: 2016 Jul
- NADPH oxidase and reactive oxygen species contribute to alcohol-induced microglial activation and neurodegeneration.
- Authors: Qin L, Crews FT
- Issue date: 2012 Jan 12