Reversible Inactivation of Superoxide‐Sensitive Aconitase in Aβ1‐42‐Treated Neuronal Cell Lines
Abstract
Abstract: The activity of the superoxide‐sensitive enzyme aconitase was monitored to evaluate the generation of superoxide in neuronal cell lines treated with β‐amyloid (Aβ) peptide 1‐42. Treatment of differentiated and undifferentiated rat PC12 and human neuroblastoma SK‐N‐SH cells with soluble Aβ1‐42 (Aβ‐derived diffusible ligands) or fibrillar Aβ1‐42 caused a 35% reversible inactivation of aconitase, which preceded loss of viability and was correlated with altered cellular function. Aconitase was reactivated upon incubation of cellular extracts with iron and sulfur, suggesting that Aβ causes the release of iron from 4Fe‐4S clusters. Aβ neurotoxicity was partially blocked by the iron chelator deferoxamine. These data suggest that increased superoxide generation and the release of iron from 4Fe‐4S clusters are early events in Aβ1‐42 neurotoxicity.
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Aβ induces production of superoxide (O2·-), nitric oxide (NO·), and multiple reactive species downstream of these radicals in many cells, including cortical neurons.
“Aβ induces production of O2·- nitric oxide (NO·), and multiple RS downstream of these radicals in many cells, including cortical neurons (Keller et al., 1998; Longo et al., 2000; Keil et al., 2004; Malinski, 2007; Stepanichev et al., 2008; Díaz et al., 2010).”
From The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer’s disease (2011) · cites this paper as Longo et al., 2000
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Self-citation
- Authors
- Longo, V. D., Viola, K. L., Klein, W. L., & Finch, C. E.
- Affiliations
- University of Southern California (US)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2000-11
- Volume
- 75
- Issue
- 5
- Pages
- 1977-1985
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1970566248
- Cited by
- 46
- References
- 9
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 2 · 2014: 1 · 2013: 1
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG-13499, R01AG013499)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- aconitase, superoxide, amyloid-beta 42, neurotoxicity, [4Fe-4S] cluster, iron release, deferoxamine, iron chelation, PC12 cells, SK-N-SH cells, oxidative stress, enzyme inactivation
- MeSH terms
- Aconitate Hydratase, Animals, Cell Differentiation, Cell Survival, Dose-Response Relationship, Drug, Enzyme Reactivators, Glycoproteins, Humans, Intracellular Fluid, Iron, Iron Chelating Agents, Ligands, Neuroblastoma, Neurons, Nitric Oxide, Peptide Fragments, Sulfur Compounds, Superoxides, Tumor Cells, Cultured, Amyloid beta-Peptides, PC12 Cells, Molecular Chaperones, Macromolecular Substances, Clusterin, Rats
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