Chonnam Med J.  2007 Aug;43(2):73-79.

Protective Effects of Epigallocatechin-3-gallate against 1-methyl-4-phenylpyridinium-induced Dopaminergic Neuronal Cell Death

• Noh HG
• Jang S
• Park SJ
• Kim SH
• Jeong HS
• Park JS

Abstract

1-methyl-4-phenylpyridinium (MPP+) is a neurotoxin that selectively inhibits the mitochondrial functions of dopaminergic neurons in the substantia nigra pars compacta. MPP+ administration is accepted as in vivo and in vitro model for Parkinson's disease (PD). In the present study, we found that MPP+ induced a concentration-dependent decrease in SN4741 mouse dopaminergic cell viability. Even though epigallocatechin-3-gallate induced a suppression of the MPP+-induced apoptosis as well as an increase of the cellular proliferation, the mechanisms underlying this process have not to be completely clarified yet. We have investigated whether EGCG plays a neuroprotective role by activating cell survival systems such as protein kinase C, and acting on the anti-apoptotic and the pro-apoptotic genes in SN4741 dopaminergic cells. EGCG restored the reduced phospho-PKC activities caused by MPP+ toxicity. In addition, gene expression analysis revealed that EGCG prevented both the MPP+-induced expression of the pro-apoptotic gene mRNA, bad and bax, and the decrease of the anti-apoptotic gene mRNA, bcl-2 and bcl-.Xl. These results suggest that the neuroprotective mechanism of EGCG against MPP+-induced apoptotic cell death includes stimulation of PKC and modulation of cell survival and death genes.

Keyword

EGCG; Neuroprotection; 1-methyl-4-phenylpyridinium; Parkinson's disease; Dopaminergic cells

MeSH Terms

1-Methyl-4-phenylpyridinium
Animals
Apoptosis
Cell Death*
Cell Proliferation
Cell Survival
Dopaminergic Neurons*
Gene Expression
Mice
Parkinson Disease
Protein Kinase C
RNA, Messenger
Substantia Nigra
1-Methyl-4-phenylpyridinium
Protein Kinase C
RNA, Messenger