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BioMed Research International
Volume 2013 (2013), Article ID 863720, 10 pages
http://dx.doi.org/10.1155/2013/863720
Research Article

7,8-Dihydroxyflavone Suppresses Oxidative Stress-Induced Base Modification in DNA via Induction of the Repair Enzyme 8-Oxoguanine DNA Glycosylase-1

1School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 690-756, Republic of Korea
2Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea
3Aging Research Center, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea
4Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea
5Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan 609-735, Republic of Korea

Received 25 May 2013; Revised 23 July 2013; Accepted 15 August 2013

Academic Editor: Peter Fu

Copyright © 2013 Ki Cheon Kim et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The modified guanine base 8-oxoguanine (8-oxoG) is abundantly produced by oxidative stress, can contribute to carcinogenesis, and can be removed from DNA by 8-oxoguanine DNA glycosylase-1 (OGG1), which acts as an 8-oxoG glycosylase and endonuclease. This study investigated the mechanism by which 7,8-dihydroxyflavone (DHF) inhibits oxidative stress-induced 8-oxoG formation in hamster lung fibroblasts (V79-4). DHF significantly reduced the amount of 8-oxoG induced by hydrogen peroxide (H2O2) and elevated the levels of OGG1 mRNA and protein. DHF increased the binding of nuclear factor erythroid 2-related factor 2 (Nrf2) to antioxidant response element sequences in the upstream promoter region of OGG1. Moreover, DHF increased the nuclear levels of Nrf2, small Maf proteins, and the Nrf2/small Maf complex, all of which are decreased by H2O2 treatment. Likewise, the level of phosphorylated Akt, which activates Nrf2, was decreased by H2O2 treatment but restored by DHF treatment. The levels of OGG1 and nuclear translocation of Nrf2 protein were decreased upon treatment with PI3K inhibitor or Akt inhibitor, and DHF treatment did not restore OGG1 and nuclear Nrf2 levels in these inhibitor-treated cells. Furthermore, PI3K and Akt inhibitors abolished the protective effects of DHF in cells undergoing oxidative stress. These data indicate that DHF induces OGG1 expression via the PI3K-Akt pathway and protects cells against oxidative DNA base damage by activating DNA repair systems.