TY - JOUR
T1 - Butin decreases oxidative stress-induced 8-hydroxy-2′-deoxyguanosine levels via activation of oxoguanine glycosylase 1
AU - Kang, Kyoung Ah
AU - Lee, Jung Hee
AU - Chae, Sungwook
AU - Zhang, Rui
AU - Piao, Mei Jing
AU - Kim, Hee Sun
AU - You, Ho Jin
AU - Hyun, Jin Won
N1 - Funding Information:
This research was performed under the program of Basic Atomic Energy Research Institute (BAERI) which is part of the Nuclear R&D Programs and in part from the study of the DNA repair regulation with the disease program [M1063901] funded by the Ministry of Science & Technology of Korea (KOSEF).
PY - 2009/10/30
Y1 - 2009/10/30
N2 - 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.
AB - 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.
KW - 8-Hydroxy-2′-deoxyguanosine
KW - Butin
KW - Oxoguanine glycosylase 1
UR - http://www.scopus.com/inward/record.url?scp=70349178640&partnerID=8YFLogxK
U2 - 10.1016/j.cbi.2009.07.011
DO - 10.1016/j.cbi.2009.07.011
M3 - Article
C2 - 19631197
AN - SCOPUS:70349178640
SN - 0009-2797
VL - 181
SP - 338
EP - 342
JO - Chemico-Biological Interactions
JF - Chemico-Biological Interactions
IS - 3
ER -
