Protein Kinase C-mediated Neuroprotective Action of (-)-epigallocatechin-3-gallate against Abeta1-42-induced Apoptotic Cell Death in SH-SY5Y Neuroblastoma Cells.
- Author:
Sujeong JANG
1
;
Kyoung Wan YOU
;
Song Hee KIM
;
Sung Jun PARK
;
Han Seong JEONG
;
Jong Seong PARK
Author Information
1. Department of Physiology, Chonnam National University Medical School, Gwangju 501-190, Korea. parkjs@jnu.ac.kr
- Publication Type:Original Article
- Keywords:
Abeta;
Alzheimer's disease;
Apoptosis;
(-)-epigallocatechin-3-gallate;
PKC
- MeSH:
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
- From:The Korean Journal of Physiology and Pharmacology
2007;11(5):163-169
- CountryRepublic of Korea
- Language:English
-
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.
