Inhibition of catalase activity with 3-amino-triazole enhances the cytotoxicity of the Alzheimer's amyloid-beta peptide.
Amyloid-beta, (Abeta) is a cytotoxic peptide implicated in the pathology of Alzheimers disease. The antioxidant enzyme catalase has been suggested to protect against Abeta 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 Abeta toxicity, suggesting that any protective role for endogenous catalase requires active enzyme. In Abeta treated mveloma cells there was a significant decrease in the total cell catalase activity and immunoreactivity. However, when the surviving live cell population was isolated following Abeta treatment the levels of catalase were significantly increased. The surviving live cell population from groups treated with both 3AT and Abeta 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 Abeta binding protein. Amyloid-beta (Abeta) cytotoxicity can be prevented by Vitamin E treatment or an anti-Abeta monoclonal antibody (ALIOI), both of which also prevent Abeta cytotoxicity in cells treated with 3AT These observations suggest that Abeta 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 Abeta is not the direct cause of cytotoxicity.
Milton
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NG
Department of Molecular Pathology and Clinical Biochemistry, Royal Free and University College Medical School, University College London, UK. nmilton@rfc.ucl.ac.uk
D000640:Amitrole / Q000633:toxicity*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000911:Antibodies, Monoclonal; D000975:Antioxidants / Q000494:pharmacology; D001932:Brain Neoplasms / Q000473:pathology; D002374:Catalase / Q000037:antagonists & inhibitors*; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000633:toxicity*; D007150:Immunohistochemistry; D051379:Mice; D009101:Multiple Myeloma / Q000473:pathology; D009474:Neurons / Q000187:drug effects; D014810:Vitamin E / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D000975:Antioxidants; D004791:Enzyme Inhibitors; D014810:Vitamin E; D002374:Catalase; D000640:Amitrole