Epigallocatechin gallate inhibits nitric oxide-induced apoptosis in rat PC12 cells

• Published in: Neuroscience letters 2007-01, Vol.411 (3), p.222-227
• Main Authors: Jung, Ji Yeon, Han, Chang Ryoung, Jeong, Yeon Jin, Kim, Hyun Jin, Lim, Hoi Soon, Lee, Ki Heon, Park, Ha Ok, Oh, Won Mann, Kim, Sun Hun, Kim, Won Jae
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; Bcl-2 family; bcl-2-Associated X Protein - metabolism; Biological and medical sciences; Blotting, Western; Caspase; Caspases - metabolism; Catechin - analogs & derivatives; Catechin - pharmacology; Cytochromes c - metabolism; Dose-Response Relationship, Drug; Drug Interactions; EGCG; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Nitric oxide; Nitric Oxide - physiology; Nitric Oxide Donors - pharmacology; Nitroprusside - pharmacology; PC12 cells; PC12 Cells - drug effects; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rats; Reactive Oxygen Species - metabolism; Tetrazolium Salts; Thiazoles; Time Factors; Vertebrates: nervous system and sense organs; Voltage-Dependent Anion Channels - metabolism
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2006.09.089

Nitric oxide (NO) is associated with many pathophysiology of the central nervous system including brain ischemia, neurodegeneration and inflammation. Epigallocatechin gallate (EGCG) is a major compound of green tea polyphenol that has shown the protective activity against neuronal diseases. This study examined the effect of EGCG on NO-induced cell death in PC12 cells. The administration of sodium nitroprusside (SNP), a NO donor, decreased the cell viability and induced apoptosis showing characterization such as cell shrinkage and chromatin condensation as well as subG1 fraction of cell cycles. EGCG inhibited the cytotoxicity and apoptotic morphogenic changes induced by SNP. EGCG attenuated the production of reactive oxygen species (ROS) by SNP, and ameliorated the SNP-induced Bax to Bcl-2 expression ratio leading to apoptosis. In addition, EGCG prevented the release of cytochrome c from the mitochondria into the cytosol as well as the upregulation of the voltage-dependent anion channel (VDAC), a cytochrome c releasing channel, in the mitochondria of SNP-treated cells. EGCG abrogated the activation of caspase-9, caspase-8 and caspase-3 induced by SNP. These results demonstrate that EGCG has a protective effect against SNP-induced apoptosis in PC12 cells by scavenging ROS and modulating the signal molecules associated with cytochrome c, caspases, VDAC and the Bcl-2 family. These findings suggest that EGCG might be a natural neuroprotective substance.