Amyloid β25–35 induced ROS-burst through NADPH oxidase is sensitive to iron chelation in microglial Bv2 cells
Abstract
Iron chelation therapy and inhibition of glial nicotinamide adenine dinucleotide phosphate (NADPH) oxidase can both represent possible routes for Alzheimer's disease modifying therapies. The metal hypothesis is largely focused on direct binding of metals to the N-terminal hydrophilic 1-16 domain peptides of Amyloid beta (Aβ) and how they jointly give rise to reactive oxygen species (ROS) production. The cytotoxic effects of Aβ through ROS and metals are mainly studied in neuronal cells using full-length Aβ1-40/42 peptides. Here we study cellularly-derived ROS during 2-60min in response to non-metal associated mid domain Aβ25-35 in microglial Bv2 cells by fluorescence based spectroscopy. We analyze if Aβ25-35 induce ROS production through NADPH oxidase and if the production is sensitive to iron chelation. NADPH oxidase inhibitor diphenyliodonium (DPI) is used to confirm the production of ROS through NADPH oxidase. We modulate cellular iron homeostasis by applying cell permeable iron chelators desferrioxamine (DFO) and deferiprone (DFP). NADPH oxidase subunit gp91-phox level was analyzed by Western blotting. Our results show that Aβ25-35 induces strong ROS production through NADPH oxidase in Bv2 microglial cells. Intracellular iron depletion resulted in restrained Aβ25-35 induced ROS.
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In neuronal cells exposed to amyloid beta peptide fragments, iron chelation with DFO or deferiprone reduces ROS generation via NADPH oxidase.
“For instance, in neuronal cells exposed to amyloid beta peptide fragments, iron chelation with DFO or deferiprone (DFP) reduces ROS generation via the NADPH oxidase [181].”
From “Pumping iron”—how macrophages handle iron at the systemic, microenvironmental, and cellular levels (2017) · cites this paper as [181]
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- Authors
- Part, K., Künnis-Beres, K., Poska, H., Land, T., Shimmo, R., & Zetterström Fernaeus, S.
- Affiliations
- Tallinn University (EE)
- Corresponding author
- Part, Kristin
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 1629
- Pages
- 282-290
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W1755191730
- Cited by
- 16
- References
- 54
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 1 · 2022: 1 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 2
- FWCI
- 1.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Estonian Ministry of Education and Science (SF0130171s08)
- Estonian Science Foundation (ETF7333, ETF7338, MJD7, MTT16)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- amyloid beta 25-35, reactive oxygen species, NADPH oxidase, iron chelation, microglia, BV-2 cells, Alzheimer's disease, deferoxamine, deferiprone, diphenyliodonium, gp91phox, iron homeostasis, oxidative stress
- MeSH terms
- Animals, Cell Line, Dose-Response Relationship, Drug, Iron, Iron Chelating Agents, Peptide Fragments, Amyloid beta-Peptides, Reactive Oxygen Species, Microglia, NADPH Oxidases, Mice
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