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 beta-peptide (A beta) 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 A beta(1-40), indicating oxidative damage of proteins. We report that neurons, subjected to A beta(1-40), respond to A beta oxidative impact by activation of antioxidant defense mechanisms and alternative ATP-generating 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) BE activity, which is the key enzyme for functioning of the creatine/ phosphocreatine shuttle, was compensated in neurons surviving the A beta oxidative attack by increased production of the enzyme. As soon as the oxidative attack triggered by the addition of preaggregated A beta(1-40) to rat hippocampal cell cultures has been extinguished, CK BE 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 BE production together with the induction of antioxidant enzyme gene expression in A beta-treated hippocampal neurons accounts for at least part of their adaptation to A beta toxicity.