Inhibitory effect of green tea extract on beta-amyloid-induced PC12 cell death by inhibition of the activation of NF-kappaB and ERK/p38 MAP kinase pathway through antioxidant mechanisms.
Beta-amyloid peptide (Abeta) is considered responsible for the pathogenesis of Alzheimer's disease (AD). Several lines of evidence support that Abeta-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 Abeta-induced oxidative cell death in cultured rat pheochromocytoma (PC12) cells. PC12 cells treated with Abeta25-35 (10-50 microM) showed intracellular ROS elevation, the formation of 8-oxodG (an oxidized form of DNA), and underwent apoptotic cell death in a dose-dependent manner. Abeta(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 microg/ml) dose-dependently attenuated Abeta(25-35) (50 microM)-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 Abeta(25-35)-induced activations of the NF-kappaB 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.
Lee
Sun Young
SY
College of Pharmacy, Chungbuk National University, 48, Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, South Korea.
Lee
Jae Woong
JW
Lee
Heesoon
H
Yoo
Han Soo
HS
Yun
Yeo Pyo
YP
Oh
Ki Wan
KW
Ha
Tae Youl
TY
Hong
Jin Tae
JT
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D028241:Camellia sinensis; D016923:Cell Death / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D017931:DNA Primers; D004789:Enzyme Activation; D016328:NF-kappa B / Q000378:metabolism*; D016716:PC12 Cells; D010673:Pheochromocytoma; D010936:Plant Extracts / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D017931:DNA Primers; D016328:NF-kappa B; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D048051:p38 Mitogen-Activated Protein Kinases