Amyloid β-peptide(1-40)-mediated oxidative stress in cultured hippocampal neurons: Protein carbonyl formation, CK BB expression, and the level of Cu, Zn, and Mn SOD mRNA

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.