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• W2024246194 endingPage "122" @default.
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• W2024246194 abstract "Increasing evidence implicates oxidative stress as partially responsible for the neurodegenerative process of Alzheimer's disease (AD). Recent reports show an increased production of nitrotyrosine in AD brains, suggesting that peroxynitrite is produced in excess in this disease. Furthermore, incidence of cerebral amyloid angiopathy in AD cases is very frequent (83%), strongly suggesting a vascular component of AD pathogenesis. We have evaluated the hypothesis that peroxynitrite could be responsible for mediating the cytotoxicity and vasoactivity induced by the amyloid-beta1-40 (Abeta) peptide. Rat brain endothelial cells (RBE-4) appear to be sensitive to Abeta-induced toxicity but not to the cytotoxicity induced by peroxynitrite. Addition of Cu/Zn superoxide dismutase to cell culture media, which is only able to clear extracellular superoxide, was not effective in blocking Abeta-induced toxicity. However, we were able to partially block Abeta-induced cytotoxicity by using Mn(III)tetrakis(4-benzoic acid) porphyrin (MnTBAP) which dismutes superoxide intracellularily. Yet, MnTBAP was not able to prevent the vasoactivity triggered by Abeta. Moreover, addition of peroxynitrite to rat aortae did not modulate the vasotension induced by Abeta. We conclude that intracellular superoxide radicals may contribute to Abeta-induced cytotoxicity. Our results also indicate that peroxynitrite does not significantly contribute to Abeta-induced cytotoxicity in rat brain endothelial cells (RBE-4) or vasoactivity in rat aortae. These results suggest that therapeutic efforts aimed at removal of reactive oxygen species with SOD is unlikely to be beneficial for treatment of Abeta-induced endothelial dysfunction. However, compounds that clear free radicals intracellularly may well be beneficial." @default.
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• W2024246194 date "1998-07-01" @default.
• W2024246194 modified "2023-09-24" @default.
• W2024246194 title "Role of Peroxynitrite in the Vasoactive and Cytotoxic Effects of Alzheimer's β-Amyloid1–40Peptide" @default.
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• W2024246194 doi "https://doi.org/10.1006/exnr.1998.6828" @default.
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