8-hydroxydeoxyguanosine suppresses NO production and COX-2 activity via Rac1/STATs signaling in LPS-induced brain microglia

被引：57
作者：
Kim, Hong Sook
Ye, Sang-Kyu
Cho, Ik Hyun
Jung, Joo Eun
Kim, Dong-Hyun
Choi, Seongwon
Kim, Yong-Sik
Park, Chung-Gyu
Kim, Tae-Yoon
Lee, Jung Weon
Chung, Myung-Hee
机构：
[1] Seoul Natl Univ, Coll Med, Dept Pharmacol, Seoul 110799, South Korea
[2] Seoul Natl Univ, Coll Dent, Dept Physiol, Seoul, South Korea
[3] Seoul Natl Univ, Inst Dent Res, Seoul, South Korea
[4] Seoul Natl Univ, Coll Med, Dept Microbiol, Seoul 110744, South Korea
[5] Catholic Univ Korea, Coll Med, Dept Dermatol, Seoul, South Korea
[6] Seoul Natl Univ, Coll Med, Dept Tumor Biol, Inst Canc Res, Seoul, South Korea
来源：
FREE RADICAL BIOLOGY AND MEDICINE | 2006年 / 41卷 / 09期
关键词：
8-hydroxydeoxyguanosine; NADPH oxidase; Rac1; STATs; iNOS; COX-2; free radicals;
D O I：
10.1016/j.freeradbiomed.2006.07.018
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Free 8-hydroxydeoxyguanosine (oh(8)dG), a nucleoside of 8-hydroxyguanine (oh(8)Gua), present in cytosol is not incorporated into DNA. However, nothing is known about its biological function when it presents in cytosol as a free form. We demonstrate here for the first time that oh(8)dG inhibits lipopolysaccharide (LPS)-induced nitric oxide (NO) production and cyclooxygenase-2 (COX-2) activity, and both gene transcriptions in microglia. Furthermore, oh(8)dG reduced mRNA levels of pro-inflammatory cytokine, such as IL-1 beta, IL-6, and TNF-alpha, in activated BV2 cells. We also found that oh(8)dG suppressed reactive oxygen species (ROS) production through reduction of NADPH oxidase activity and blocked Rac1/STATs signal cascade. Finally, oh(8)dG suppressed recruitment of STATs and p300 to the iNOS and COX-2 promoters, and inhibited H3 histone acetylation. Taken together, these results provide new aspects of oh(8)dG as an anti-inflammatory agent. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码：1392 / 1403
页数：12
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