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, F., Ferri, A., Casciati, A., D'Ambrosi, N., Rotilio, G., Costa, A., et al. (2004). Overexpression of superoxide dismutase 1 protects against beta-amyloid peptide toxicity: effect of estrogen and copper chelators. NEUROCHEMISTRY INTERNATIONAL, 44(1), 25-33 [10.1016/S0197-0186(03)00101-3].

Overexpression of superoxide dismutase 1 protects against beta-amyloid peptide toxicity: effect of estrogen and copper chelators

D'Ambrosi, N;ROTILIO, GIUSEPPE;CARRI', MARIA TERESA
2004-01-01

Abstract

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.
gen-2004
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10 - BIOCHIMICA
English
Con Impact Factor ISI
Superoxide Dismutase; Apoptosis; Electrophoresis, Polyacrylamide Gel; Thiazoles; Humans; Caspase 3; Cell Differentiation; Tetrazolium Salts; Caspase 1; Fluorescent Dyes; Copper; Reactive Oxygen Species; Caspases; Neuroblastoma; Estradiol; Benzimidazoles; Brain Neoplasms; Coloring Agents; Blotting, Western; Tumor Cells, Cultured; Amyloid beta-Peptides; Chelating Agents; Fluorescent Antibody Technique; Cell Line
Celsi, F., Ferri, A., Casciati, A., D'Ambrosi, N., Rotilio, G., Costa, A., et al. (2004). Overexpression of superoxide dismutase 1 protects against beta-amyloid peptide toxicity: effect of estrogen and copper chelators. NEUROCHEMISTRY INTERNATIONAL, 44(1), 25-33 [10.1016/S0197-0186(03)00101-3].
Celsi, F; Ferri, A; Casciati, A; D'Ambrosi, N; Rotilio, G; Costa, A; Volonté, C; Carri', Mt
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/31847
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