Amyloid beta-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-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 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 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 A beta-treated hippocampal neurons accounts for at least part of their adaptation to A beta toxicity.
Sanders-Brown Center on Aging, University of Kentucky, Lexington, USA.
M Y
MY
Aksenov
M V
MV
Aksenova
W R
WR
Markesbery
D A
DA
Butterfield
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000196:embryology; D006801:Humans; D007527:Isoenzymes; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010446:Peptide Fragments / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics*; D013778:Tetrazolium Salts / Q000032:analysis; D013844:Thiazoles / Q000032:analysis; D014343:Trypan Blue / Q000378:metabolism
D016229:Amyloid beta-Peptides; D007527:Isoenzymes; D010446:Peptide Fragments; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); D013482:Superoxide Dismutase; D003402:Creatine Kinase; C022616:thiazolyl blue; D014343:Trypan Blue