| Autor: |
Kumita, Janet, Manucat-Tan, Noralyn, Chowdhury, Ashfaq, Cataldi, Rodrigo, Zeinnedine-Abdullah, Rafaa, Wyatt, Amy |
| Přispěvatelé: |
Kumita, Janet [0000-0002-3887-4964], Apollo - University of Cambridge Repository |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Redox Biology. 63:102736 |
| ISSN: |
2213-2317 |
| DOI: |
10.1016/j.redox.2023.102736 |
| Popis: |
Myeloperoxidase, the enzyme that produces hypochlorite (OCl-), is expressed by brain-resident immune cells and neurons. In this study we characterise the effects of hypochlorite on the aggregation and toxicity of amyloid beta peptide 1-42 (Aβ1-42), a major component of amyloid plaques that form in the brain in Alzheimer’s disease. Our results demonstrate that treatment with hypochlorite promotes the formation of Aβ1-42 assemblies ≥ 100 kDa that have reduced surface exposed hydrophobicity compared to the untreated peptide. This effect is the result of the oxidation of Aβ1-42 at a single site as determined by mass spectrometry analysis. Although treatment with hypochlorite promotes the aggregation of Aβ1-42, the solubility of the peptide is enhanced and amyloid fibril formation is inhibited as assessed by filter trap assay, thioflavin T assay and transmission electron microscopy. The results of in vitro assays using SH-SY5Y neuroblastoma cells show that pre-treatment of Aβ1-42 with a sub-stoichiometric amount of hypochlorite substantially reduces its toxicity. The results of flow cytometry analysis and internalization assays show that hypochlorite-induced modification of Aβ1-42 reduces its binding to the surface of SH-SY5Y cells and concomitantly, increases the efficiency of Aβ1-42 endocytosis. Our data is consistent with a model in which tightly regulated production of hypochlorite in the brain is protective against Aβ-induced toxicity. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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