title: Butin (7,3',4'-trihydroxydihydroflavone) reduces oxidative stress-induced cell death via inhibition of the mitochondria-dependent apoptotic pathway.
abstract: Recently, we demonstrated that butin (7,3',4'-trihydroxydihydroflavone) protected cells against hydrogen peroxide (H(2)O(2))-induced apoptosis by: (1) scavenging reactive oxygen species (ROS), activating antioxidant enzymes such superoxide dismutase and catalase; (2) decreasing oxidative stress-induced 8-hydroxy-2'-deoxyguanosine levels via activation of oxoguanine glycosylase 1, and (3), reducing oxidative stress-induced mitochondrial dysfunction. The objective of this study was to determine the cytoprotective effects of butin on oxidative stress-induced mitochondria-dependent apoptosis, and possible mechanisms involved. Butin significantly reduced H(2)O(2)-induced loss of mitochondrial membrane potential as determined by confocal image analysis and flow cytometry, alterations in Bcl-2 family proteins such as decrease in Bcl-2 expression and increase in Bax and phospho Bcl-2 expression, release of cytochrome c from mitochondria into the cytosol and activation of caspases 9 and 3. Furthermore, the anti-apoptotic effect of butin was exerted via inhibition of mitogen-activated protein kinase kinase-4, c-Jun NH(2)-terminal kinase (JNK) and activator protein-1 cascades induced by H(2)O(2) treatment. Finally, butin exhibited protective effects against H(2)O(2)-induced apoptosis, as demonstrated by decreased apoptotic bodies, sub-G(1) hypodiploid cells and DNA fragmentation. Taken together, the protective effects of butin against H(2)O(2)-induced apoptosis were exerted via blockade of membrane potential depolarization, inhibition of the JNK pathway and mitochondria-involved caspase-dependent apoptotic pathway.
authors: School of Medicine and Applied Radiological Science Research Institute, Jeju National University, Jeju-si 690-756, Korea; E-Mails: zhangrui26@hotmail.com (R.Z.); meijing0219@hotmail.com (M.J.P.); svv771@hotmail.com (K.C.K.); candy4860@hanmail.net (A.D.K.).
authors: Rui
authors: R
authors: Zhang
authors: In Kyung
authors: IK
authors: Lee
authors: Mei Jing
authors: MJ
authors: Piao
authors: Ki Cheon
authors: KC
authors: Kim
authors: Areum Daseul
authors: AD
authors: Kim
authors: Hye Sun
authors: HS
authors: Kim
authors: Sungwook
authors: S
authors: Chae
authors: Hee Sun
authors: HS
authors: Kim
authors: Jin Won
authors: JW
authors: Hyun
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D048768:MAP Kinase Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001578:Benzopyrans; D019253:Proto-Oncogene Proteins c-bcl-2; D018808:Transcription Factor AP-1; C051437:butin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D048031:JNK Mitogen-Activated Protein Kinases; D048768:MAP Kinase Kinase Kinase 4; D003849:Deoxyguanosine