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Open AccessArticle

Triphlorethol-A from Ecklonia cava Up-Regulates the Oxidant Sensitive 8-Oxoguanine DNA Glycosylase 1

School of Medicine, Jeju National University, Jeju 690-756, Korea
Radiation Effect Research Team, Radiation Health Research Institute, Korea Hydro & Nuclear Power Co., LTD., Seoul 135-881, Korea
Food and Nutrition, Duksung Women's University, Seoul 132-714, Korea
Department of Chemistry, College of Natural Sciences, Jeju National University, Jeju 690-756, Korea
Author to whom correspondence should be addressed.
Mar. Drugs 2014, 12(11), 5357-5371;
Received: 10 July 2014 / Revised: 2 October 2014 / Accepted: 14 October 2014 / Published: 28 October 2014
This study investigated the protective mechanisms of triphlorethol-A, isolated from Ecklonia cava, against oxidative stress-induced DNA base damage, especially 8-oxoguanine (8-oxoG), in Chinese hamster lung fibroblast V79-4 cells. 8-Oxoguanine DNA glycosylase-1 (OGG1) plays an important role in the removal of 8-oxoG during the cellular response to DNA base damage. Triphlorethol-A significantly decreased the levels of 8-oxoG induced by H2O2, and this correlated with increases in OGG1 mRNA and OGG1 protein levels. Furthermore, siOGG1-transfected cell attenuated the protective effect of triphlorethol-A against H2O2 treatment. Nuclear factor erythroid 2–related factor 2 (Nrf2) is a transcription factor for OGG1, and Nrf2 combines with small Maf proteins in the nucleus to bind to antioxidant response elements (ARE) in the upstream promoter region of the OGG1 gene. Triphlorethol-A restored the expression of nuclear Nrf2, small Maf protein, and the Nrf2-Maf complex, all of which were reduced by oxidative stress. Furthermore, triphlorethol-A increased Nrf2 binding to ARE sequences and the resulting OGG1 promoter activity, both of which were also reduced by oxidative stress. The levels of the phosphorylated forms of Akt kinase, downstream of phosphatidylinositol 3-kinase (PI3K), and Erk, which are regulators of OGG1, were sharply decreased by oxidative stress, but these decreases were prevented by triphlorethol-A. Specific PI3K, Akt, and Erk inhibitors abolished the cytoprotective effects of triphlorethol-A, suggesting that OGG1 induction by triphlorethol-A involves the PI3K/Akt and Erk pathways. Taken together, these data indicate that by activating the DNA repair system, triphlorethol-A exerts protective effects against DNA base damage induced by oxidative stress. View Full-Text
Keywords: antioxidant response elements; 8-oxoguanine; Nrf2; OGG1; Triphlorethol-A antioxidant response elements; 8-oxoguanine; Nrf2; OGG1; Triphlorethol-A
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Kim, K.C.; Lee, I.K.; Kang, K.A.; Piao, M.J.; Ryu, M.J.; Kim, J.M.; Lee, N.H.; Hyun, J.W. Triphlorethol-A from Ecklonia cava Up-Regulates the Oxidant Sensitive 8-Oxoguanine DNA Glycosylase 1. Mar. Drugs 2014, 12, 5357-5371.

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