Chonnam Med J.  2006 Aug;42(2):71-78.

Neuroprotective Effects of EGCG against Amyloid-beta (1-42)-Induced Apoptosis

• Yoo EJ
• Jang SJ
• Park JS
• Jeong HS

Abstract

The neurotoxicity of amyloid beta (A beta) is associated with increased production of reactive oxygen species (ROS) and apoptosis, and it has been implicated in the development of Alzheimer's disease. While epigallocatechin-3-gallate (EGCG) suppresses A beta-induced apoptosis, the mechanisms underlying this process have yet to be completely clarified. This study was designed to investigate whether EGCG plays a neuroprotective role by activating cell survival systems such as ERK1/2, p38 MAP kinases, and phosphatidylinositol-3 kinase (PI3K), and acting on the anti-apoptotic and the pro-apoptotic genes in SHSY5Y neuroblastoma cells. 1 micrometer A beta1-42 decreased cell viability, which was correlated with increased Hoechst33343 fluorescence, DNA fragmentation under DAPI staining. Pre-treatment of SHSY5Y neuroblastoma cells with 1 micrometer EGCG significantly attenuated A beta1-42-induced cytotoxicity. Potential cell signalling candidates involved in this neuroprotective effect were further examined. EGCG restored the reduced phospho-PI3K activities caused by A beta1-42 toxicity. In addition, gene expression analysis revealed that EGCG prevented both the A beta1-42-induced expression of a pro-apoptotic gene mRNA, Bad and the decrease of an anti-apoptotic gene mRNA, Bcl-2. These results suggest that the neuroprotective mechanism of EGCG against A beta1-42-induced apoptotic cell death includes stimulation of PI3K and modulation of cell survival and death genes.

Keyword

Neuroprotection; Amyloid-beta; EGCG; Alzheimer's disease

MeSH Terms

Alzheimer Disease
Amyloid
Apoptosis*
Cell Death
Cell Survival
DNA Fragmentation
Fluorescence
Gene Expression
Neuroblastoma
Neuroprotective Agents*
Phosphotransferases
Reactive Oxygen Species
RNA, Messenger
Amyloid
Neuroprotective Agents
Phosphotransferases
RNA, Messenger
Reactive Oxygen Species