Korean J Physiol Pharmacol.  2007 Oct;11(5):163-169.

Protein Kinase C-mediated Neuroprotective Action of (-)-epigallocatechin-3-gallate against Abeta1-42-induced Apoptotic Cell Death in SH-SY5Y Neuroblastoma Cells

• Jang S
• You KW
• Kim SH
• Park SJ
• Jeong HS
• Park JS

Abstract

The neurotoxicity of amyloid beta (Abeta) is associated with an increased production of reactive oxygen species and apoptosis, and it has been implicated in the development of Alzheimer's disease. While (-)-epigallocatechin-3-gallate (EGCG) suppresses Abeta-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 system such as protein kinase C (PKC), extracellular-signal-related kinase (ERK), c-Jun N-terminal kinase (JNK), and anti-apoptotic and pro-apoptotic genes in SH-SY5Y human neuroblastoma cells. One microM Abeta1-42 decreased cell viability, which was correlated with increased DNA fragmentation evidenced by DAPI staining. Pre-treatment of SH-SY5Y neuroblastoma cells with EGCG (1microM) significantly attenuated Abeta1-42-induced cytotoxicity. Potential cell signaling candidates involved in this neuroprotective effects were further examined. EGCG restored the reduced PKC, ERK, and JNK activities caused by Abeta1-42 toxicity. In addition, gene expression analysis revealed that EGCG prevented both the Abeta1-42-induced expression of a pro-apoptotic gene mRNA, Bad and Bax, and the decrease of an anti-apoptotic gene mRNA, Bcl-2 and Bcl-xl. These results suggest that the neuroprotective mechanism of EGCG against Abeta1-42-induced apoptotic cell death includes stimulation of PKC, ERK, and JNK, and modulation of cell survival and death genes.

Keyword

Abeta; Alzheimer's disease; Apoptosis; (-)-epigallocatechin-3-gallate; PKC

MeSH Terms

Alzheimer Disease
Amyloid
Apoptosis
Cell Death*
Cell Survival
DNA Fragmentation
Gene Expression
Humans
JNK Mitogen-Activated Protein Kinases
Neuroblastoma*
Neuroprotective Agents
Phosphotransferases
Protein Kinase C
Protein Kinases*
Reactive Oxygen Species
RNA, Messenger
Amyloid
JNK Mitogen-Activated Protein Kinases
Neuroprotective Agents
Phosphotransferases
Protein Kinase C
Protein Kinases
RNA, Messenger
Reactive Oxygen Species