Korean J Physiol Pharmacol.  2005 Aug;9(4):239-246.

Inhibition of Nitric Oxide-induced Neuronal Apoptosis in PC12 Cells by Epigallocatechin Gallate

• Jung JY
• Jeong YJ
• Han CR
• Kim SH
• Kim HJ
• Lee KH
• Park HO
• Kim WJ

Abstract

In the central nervous system, nitric oxide (NO) is associated with many pathological diseases such as brain ischemia, neurodegeneration and inflammation. The epigallocatechin gallate (EGCG), a major compound of green tea, is recognized as protective substance against neuronal diseases. This study is aimed to investigate the effect of EGCG on NO-induced cell death in PC12 cells. Administration of sodium nitroprusside (SNP), a NO donor, decreased cell viability in a dose- and time-dependent manner and induced genomic DNA fragmentation with cell shrinkage and chromatin condensation. EGCG diminished the decrement of cell viability and the formation of apoptotic morphologenic changes as well as DNA fragmentation by SNP. EGCG played as an antioxidant that attenuated the production of reactive oxygen species (ROS) by SNP. The cells treated with SNP showed downregulation of Bcl-2, but upregulation of Bax. EGCG ameliorated the altered expression of Bcl-2 and Bax by SNP. The release of cytochrome c from mitochondria into cytosol and expression of voltage -dependent anion channel (VDAC) 1, a cytochrome c releasing channel in mitochondria, were increased in SNP-treated cells, whereas were attenuated by EGCG. The enhancement of caspase-9, preceding mitochondria-dependent pathway, caspase-8 and death receptor-dependent pathway, as well as caspase-3 activities were suppressed by EGCG. SNP upragulated Fas and Fas-L, which are death receptor assembly, whereas EGCG ameliorated the expression of Fas enhanced by SNP. These results demonstrated that EGCG has a protective effect against SNP-induced apoptosis in PC12 cells, through scavenging ROS and regulating the mitocondria- and death receptor-mediated signal pathway. The present study suggest that EGCG might be a natural neuroprotective substance.

Keyword

Nitric oxide; PC12 cell; Apoptosis; Caspase; Bcl-2 family; EGCG

MeSH Terms

Animals
Apoptosis*
Brain Ischemia
Caspase 3
Caspase 8
Caspase 9
Cell Death
Cell Survival
Central Nervous System
Chromatin
Cytochromes c
Cytosol
DNA Fragmentation
Down-Regulation
Humans
Inflammation
Mitochondria
Neurons*
Nitric Oxide
Nitroprusside
PC12 Cells*
Reactive Oxygen Species
Signal Transduction
Tea
Tissue Donors
Up-Regulation
Caspase 3
Caspase 8
Caspase 9
Chromatin
Cytochromes c
Nitric Oxide
Nitroprusside
Reactive Oxygen Species
Tea