Overexpression of superoxide dismutase 1 protects against beta-amyloid peptide toxicity: effect of estrogen and copper chelators.
Beta-amyloid peptides (Abeta) are major constituents of senile plaques in Alzheimer's disease (AD) brain and contribute to neurodegeneration, operating through activation of apoptotic pathways. It has been proposed that Abeta induces death by oxidative stress, possibly through the generation of peroxynitrite from superoxide and nitric oxide. Estrogen is thought to play a protective role against neurodegeneration through a variety of mechanisms including scavenging of reactive oxygen species (ROS). In this study, we have challenged with Abeta, either in the presence or in the absence of 17beta-estradiol, differentiated human neuroblastoma SH-SY5Y cells (named line SH) and the same line overexpressing anti-oxidant enzyme superoxide dismutase 1 (SOD1; named line WT). We have observed that: (1) WT cells are less susceptible than SH cells to Abeta insult; (2) caspase-3, but not caspase-1, is involved in Abeta-induced apoptosis in this system; (3) estrogen protects both lines, without significantly affecting SOD activity; and (4) copper chelators prevent Abeta-induced toxicity. Our results further support the notion that anti-oxidant therapy might be beneficial in the treatment of AD by preventing activation of selected apoptotic pathways.
Celsi
Fulvio
F
Fondazione Santa Lucia IRCCS, Rome, Italy.
Ferri
Alberto
A
Casciati
Arianna
A
D'Ambrosi
Nadia
N
Rotilio
Giuseppe
G
Costa
Alfredo
A
Volonté
Cinzia
C
Carrì
Maria Teresa
MT
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D017209:Apoptosis / Q000502:physiology; D001562:Benzimidazoles; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology*; D004396:Coloring Agents; D003300:Copper; D004591:Electrophoresis, Polyacrylamide Gel; D004958:Estradiol / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000502:physiology*; D000072105:Superoxide Dismutase-1; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D001562:Benzimidazoles; D002614:Chelating Agents; D004396:Coloring Agents; D005456:Fluorescent Dyes; D017382:Reactive Oxygen Species; C000606290:SOD1 protein, human; D013778:Tetrazolium Salts; D013844:Thiazoles; D004958:Estradiol; D003300:Copper; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1; C022616:thiazolyl blue; C017807:bisbenzimide ethoxide trihydrochloride