Inhibition of catalase activity with 3-amino-triazole enhances the cytotoxicity of the Alzheimer's amyloid-β peptide

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Abstract

Amyloid-β (Aβ) is a cytotoxic peptide implicated in the pathology of Alzheimers disease. The antioxidant enzyme catalase has been suggested to protect against Aβ cytotoxicity in both neuronal and non-neuronal cell types. Inhibition of endogenous catalase using 3-amino-1,2,4-triazole (3AT) in neuronal (NT-2) and myeloma (SP2/0-Ag-14) cell lines increases Aβ toxicity, suggesting that any protective role for endogenous catalase requires active enzyme. In Aβ treated myeloma cells there was a significant decrease in the total cell catalase activity and immunoreactivity. However, when the surviving live cell population was isolated following Aβ treatment the levels of catalase were significantly increased. The surviving live cell population from groups treated with both 3AT and Aβ contain elevated immunoreactive catalase levels suggesting that the protective role for endogenous catalase may have a component independent of the antioxidant activity, possibly by acting as an Aβ binding protein. Amyloid-β (Aβ) cytotoxicity can be prevented by Vitamin E treatment or an anti-Aβ monoclonal antibody (ALI01), both of which also prevent Aβ cytotoxicity in cells treated with 3AT. These observations suggest that Aβ mediated cell death in both neuronal and non-neuronal cells is mediated in part by actions to increase hydrogen peroxide. Catalase has a protective role, as a hydrogen peroxide-degrading enzyme and catalase inhibition by Aβ is not the direct cause of cytotoxicity.

Original languageEnglish
Pages (from-to)767-774
Number of pages8
JournalNeuroToxicology
Volume22
Issue number6
DOIs
Publication statusPublished - 1 Dec 2001
Externally publishedYes

Keywords

  • 3-Amino-1,2,4-triazole
  • Alzheimer's disease
  • Amyloid-β (Aβ)
  • Catalase
  • Myeloma cells
  • NT-2 neurons

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