Butin decreases oxidative stress-induced 8-hydroxy-2'-deoxyguanosine levels via activation of oxoguanine glycosylase 1.
In response to oxidative DNA base damage, oxoguanine glycosylase 1 (OGG1), in a base-excision repair (BER) pathway in mammals, plays a vital role in the repair of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which is a reliable marker of reactive oxygen species (ROS)-induced DNA base modification and contributes to the pathologic process of cancer. Recently, we have shown that butin (7,3',4'-trihydroxydihydroflavone) protects cells against hydrogen peroxide (H2O2)-induced damage of cellular components including DNA. In the present study, we examined the possible protective effect of butin on oxidative stress-induced DNA base modification, especially 8-OHdG. Hydrogen peroxide significantly increased the level of 8-OHdG, which was detected by 8-OHdG ELISA and confocal microscopy, but butin decreased this level. Suppression of 8-OHdG formation by butin was related to the enhanced mRNA and protein expression of OGG1, which was detected by RT-PCR and Western blot analysis. Butin also increased the transcriptional activity of OGG1, which was suppressed by H2O2 treatment; this transcriptional activity was detected by OGG1 promoter luciferase assay. Butin enhanced the expression of phosphorylated Akt (active form of Akt), a regulator of OGG1, which was decreased by H2O2 treatment. A PI3K-specific inhibitor, LY294002, abolished the phosphorylated Akt and OGG1 expressions induced by butin, suggesting that OGG1 induction by butin involves the PI3K/Akt pathway.
Kang
Kyoung Ah
KA
School of Medicine and Applied Radiological Science Research Institute, Jeju National University, Daehakno, Jeju-si 690-756, Republic of Korea.
Lee
Jung Hee
JH
Chae
Sungwook
S
Zhang
Rui
R
Piao
Mei Jing
MJ
Kim
Hee Sun
HS
You
Ho Jin
HJ
Hyun
Jin Won
JW
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001483:Base Sequence; D001578:Benzopyrans / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004789:Enzyme Activation; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001578:Benzopyrans; D017931:DNA Primers; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C051437:butin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt; D045647:DNA Glycosylases; D003849:Deoxyguanosine