Epigallocatechin gallate inhibits nitric oxide-induced apoptosis in rat PC12 cells.
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.
Jung
Ji Yeon
JY
Dental Science Research Institute, School of Dentistry, 2nd Stage of Brain Korea 21 for School of Dentistry, Chonnam National University, Gwangju 500-757, South Korea.
Han
Chang Ryoung
CR
Jeong
Yeon Jin
YJ
Kim
Hyun Jin
HJ
Lim
Hoi Soon
HS
Lee
Ki Heon
KH
Park
Ha Ok
HO
Oh
Won Mann
WM
Kim
Sun Hun
SH
Kim
Won Jae
WJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D016716:PC12 Cells / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000975:Antioxidants; C494828:Bax protein, rat; D020030:Nitric Oxide Donors; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D050994:Voltage-Dependent Anion Channels; D051028:bcl-2-Associated X Protein; D009599:Nitroprusside; D009569:Nitric Oxide; D002392:Catechin; D045304:Cytochromes c; C045651:epigallocatechin gallate; D020169:Caspases; C022616:thiazolyl blue