Protective effects of vitamin E against oxidative damage induced by Abeta1-40Cu(II) complexes.
beta-amyloid peptide (Abeta) is considered to be responsible for the formation of senile plaques, which is the hallmark of Alzheimer's disease (AD). Oxidative stress, manifested by protein oxidation and lipid peroxidation, among other alterations, is a characteristic of AD brain. A growing body of evidence has been presented in support of Abeta(1-40) forming an oligomeric complex that binds copper at a CuZn superoxide dismutase-like binding site. Abeta(1-40)Cu(II) complexes generate neurotoxic hydrogen peroxide (H(2)O(2)) from O(2) via Cu(2+) reduction, though the precise reaction mechanism is unclear. The toxicity of Abeta(1-40) or the Abeta(1-40)Cu(II) complexes to cultured primary cortical neurons was partially attenuated when (+)-alpha-tocopherol (vitamin E) as free radical antioxidant was added at a concentration of 100 mM. The data derived from lactate dehydrogenase (LDH) release and the formation of H(2)O(2) confirmed the results from the MTT assay. These findings indicate that copper binding to Abeta(1-40) can give rise to greater production of H(2)O(2), which leads to a breakdown in the integrity of the plasma membrane and subsequent neuronal death. Groups treated with vitamin E exhibited much slighter damage, suggesting that vitamin E plays a key role in protecting neuronal cells from dysfunction or death.
Dai
Xueling
X
College of Applied Sciences and Humanities of Beijing Union University, Beijing 100083, China.
Sun
Yaxuan
Y
Jiang
Zhaofeng
Z
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D003300:Copper / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000032:analysis / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D014810:Vitamin E; D003300:Copper; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase