Protective effect of resveratrol on β-amyloid-induced oxidative PC12 cell death

• Published in: Free radical biology & medicine 2003-04, Vol.34 (8), p.1100-1110
• Main Authors: Jang, Jung-Hee, Surh, Young-Joon
• Format: Article
• Language: English
• Subjects: Amyloid beta-Peptides - metabolism; Animals; Antioxidants - pharmacology; Apoptosis; bcl-2-Associated X Protein; Beta-amyloid; Blotting, Western; Cell Death; Cell Nucleus - metabolism; Cell Survival; Coloring Agents - pharmacology; Dose-Response Relationship, Drug; Free radicals; In Situ Nick-End Labeling; Membrane Potentials; Microscopy, Fluorescence; Mitochondria - metabolism; NF-kappa B - metabolism; NF-κB; Oxidative Stress; Oxygen - metabolism; PC12 Cells; Peroxides - metabolism; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-bcl-2; Rats; Reactive oxygen intermediates; Reactive Oxygen Species; Resveratrol; Signal Transduction; Stilbenes - pharmacology; Tetrazolium Salts - pharmacology; Thiazoles - pharmacology; Vitaceae
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/S0891-5849(03)00062-5

Beta-amyloid peptide is considered to be responsible for the formation of senile plaques that accumulate in the brains of patients with Alzheimer’s disease. There has been compelling evidence supporting the idea that β-amyloid-induced cytotoxicity is mediated through the generation of reactive oxygen intermediates (ROIs). Considerable attention has been focused on identifying phytochemicals that are able to scavenge excess ROIs, thereby protecting against oxidative stress and cell death. Resveratrol (3,5,4′-trihydroxy- trans-stilbene), a phytoalexin found in the skin of grapes, has strong antioxidative properties that have been associated with the protective effects of red wine consumption against coronary heart disease (“the French paradox”). In this study, we have investigated the effects of resveratrol on β-amyloid-induced oxidative cell death in cultured rat pheochromocytoma (PC12) cells. PC12 cells treated with β-amyloid exhibited increased accumulation of intracellular ROI and underwent apoptotic death as determined by characteristic morphological alterations and positive in situ terminal end-labeling (TUNEL staining). Beta-amyloid treatment also led to the decreased mitochondrial membrane potential, the cleavage of poly(ADP-ribose)polymerase, an increase in the Bax/Bcl-X L ratio, and activation of c-Jun N-terminal kinase. Resveratrol attenuated β-amyloid-induced cytotoxicity, apoptotic features, and intracellular ROI accumulation. Beta-amyloid transiently induced activation of NF-κB in PC12 cells, which was suppressed by resveratrol pretreatment.