Inhibitory effect of green tea extract on β-amyloid-induced PC12 cell death by inhibition of the activation of NF-κB and ERK/p38 MAP kinase pathway through antioxidant mechanisms

Abstract

Beta-amyloid peptide (Aβ) is considered responsible for the pathogenesis of Alzheimer's disease (AD). Several lines of evidence support that Aβ-induced cytotoxicity is mediated through the generation of reactive oxygen species (ROS). Thus, agents that scavenge ROS level may usefully impede the development or progress of AD. Green tea extract has been known to have such antioxidant properties. Our previous studies demonstrate that green tea extract protected ischemia/reperfusion-induced brain cell death by scavenging oxidative damages of macromolecules. In this study, we investigated the effects of green tea extract on Aβ-induced oxidative cell death in cultured rat pheochromocytoma (PC12) cells. PC12 cells treated with Aβ_25–35 (10–50 μM) showed intracellular ROS elevation, the formation of 8-oxodG (an oxidized form of DNA), and underwent apoptotic cell death in a dose-dependent manner. Aβ_25–35 treatment upregulated pro-apoptotic p53 at the gene level, and Bax and caspase-3 at the protein level, but downregulated anti-apoptotic Bcl-2 protein. Interestingly, co-treated green tea extract (10–50 μg/ml) dose-dependently attenuated Aβ_25–35 (50 μM)-induced cell death, intracellular ROS levels, and 8-oxodG formation, in addition to p53, Bax, and caspase-3 expression, but upregulated Bcl-2. Furthermore, green tea extract prevented the Aβ_25–35-induced activations of the NF-κB and ERK and p38 MAP kinase pathways. Our study suggests that green tea extract may usefully prevent or retard the development and progression of AD.