Korean J Phys Anthropol.  2005 Jun;18(2):139-147.

Inhibition of Amyloid beta Peptide-induced Neuronal Cytotoxicity by EGCG

• Kim MS
• Jung JY
• Kim EC
• Kim HJ
• Kim WJ
• Lee EJ
• Kim SH

Abstract

This study is aimed to investigate the signal transduction pathway of amyloid beta peptide (Abeta)-induced neuronal toxicity and the inhibitory effects of epigallocatechin gallate (EGCG), one of the major constituents of green-tea and the potent anti-oxidant, on the nerve cell damage in PC12 cells. Cellular toxicity was estimated by MTT assay and observation of morphological changes in PC12 cells. By using the methods such as measurement of Reactive Oxygen Species (ROS), western blot and RT-PCR, the underlying mechanisms and signal transduction pathway of Abeta- induced neurotoxicity and the inhibitory effects of EGCG were examined. Abeta-induced cellular toxicity was found in a dose dependent manner. This is confirmed by morphological observations of cultured cells such as findings of cell death similar to apoptosis. Abeta-induced neurotoxicity was effectively inhibited by EGCG pretreatment. Moreover, EGCG reduced ROS as same potent as he NAC (N-acetyl cystein), the ROS scavenger. Among the several process of signal transduction for cell death, a intracytoplasmic cytochrome c, the protein associated with the mitochondria- dependent pathway, was increased from 12 hours after Abeta treatment and the increased cytochrome c by Abeta was blocked by EGCG. Expression levels of Bax/Bcl-2 in relation to intracytoplasmic release of cytochrome c were examined by RT-PCR. Abeta up-regulated Bax expression but did not affect Bcl-2 expression. EGCG was found to block the effect of Abeta-induced Bax increase. From these results, it is speculated that Abeta-induced neuronal toxicity may be assumed to be affected by ROS and the mitochondria-dependent pathway of cell death as well. EGCG, besides having the role of anti-oxidant, is found to have a protective effect against Abeta-induced neurotoxicity through the inhibition of the expression of the protein associated with the mitochondria-dependent cell death pathway.

Keyword

Amyloid beta peptide; PC12 cells; Epigallocatechine gallate; Cytotoxicity

MeSH Terms

Amyloid beta-Peptides
Amyloid*
Animals
Apoptosis
Blotting, Western
Cell Death
Cells, Cultured
Cytochromes c
Neurons*
PC12 Cells
Reactive Oxygen Species
Signal Transduction
Amyloid
Amyloid beta-Peptides
Cytochromes c
Reactive Oxygen Species