Amyloid β-peptide(1–40)-mediated oxidative stress in cultured hippocampal neurons
Mechanism of amyloid β-peptide (Aβ) toxicity in cultured neurons involves the development of oxidative stress in the affected cells. A significant increase in protein carbonyl formation was detected in cultured hippocampal neurons soon after the addition of preaggregated Aβ(1–40), indicating oxidative damage of proteins. We report that neurons, subjected to Aβ(1–40), respond to Aβ oxidative impact by activation of antioxidant defense mechanisms and alternative ATP-regenerating pathway. The study demonstrates an increase of Mn SOD gene expression and the restoration of Cu, Zn SOD gene expression to a normal level after temporary suppression. Partial loss of creatine kinase (CK) BB activity, which is the key enzyme for functioning of the creatine/phosphocreatine shuttle, was compensated in neurons surviving the Aβ oxidative attack by increased production of the enzyme. As soon as the oxidative attack triggered by the addition of preaggregated Aβ(1–40) to rat hippocampal cell cultures has been extinguished, CK BB expression and SOD isoenzyme-specific mRNA levels in surviving neurons return to normal.
We propose that the maintenance of a constant level of CK function by increased CK BB production together with the induction of antioxidant enzyme gene expression in Aβ-treated hippocampal neurons accounts for at least part of their adaptation to Aβ toxicity.
Index EntriesAmyloid β-peptide oxidative stress protein carbonyls CK BB SOD
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