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

Hong Sook Kim; Sang Kyu Ye; Ik Hyun Cho; Joo Eun Jung; Dong Hyun Kim; Seongwon Choi; Yong Sik Kim; Chung Gyu Park; Tae Yoon Kim; Jung Weon Lee; Myung Hee Chung

doi:10.1016/j.freeradbiomed.2006.07.018

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

Hong Sook Kim
, Sang Kyu Ye
, Ik Hyun Cho
, Joo Eun Jung
, Dong Hyun Kim
, Seongwon Choi
, Yong Sik Kim
, Chung Gyu Park
, Tae Yoon Kim
, Jung Weon Lee
, Myung Hee Chung

Research output: Contribution to journal › Article › peer-review

59 Citations (Scopus)

Abstract

Free 8-hydroxydeoxyguanosine (oh⁸dG), a nucleoside of 8-hydroxyguanine (oh⁸Gua), 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 oh⁸dG inhibits lipopolysaccharide (LPS)-induced nitric oxide (NO) production and cyclooxygenase-2 (COX-2) activity, and both gene transcriptions in microglia. Furthermore, oh⁸dG reduced mRNA levels of pro-inflammatory cytokine, such as IL-1β, IL-6, and TNF-α, in activated BV2 cells. We also found that oh⁸dG suppressed reactive oxygen species (ROS) production through reduction of NADPH oxidase activity and blocked Rac1/STATs signal cascade. Finally, oh⁸dG 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 oh⁸dG as an anti-inflammatory agent.

Original language	English
Pages (from-to)	1392-1403
Number of pages	12
Journal	Free Radical Biology and Medicine
Volume	41
Issue number	9
DOIs	https://doi.org/10.1016/j.freeradbiomed.2006.07.018
Publication status	Published - 1 Nov 2006

Bibliographical note

Funding Information:
This study was supported by a grant of the Korea Health 21 R and D Project, Ministry of Health and Welfare (Project No.: A040004), and the Ministry of Science and Technology of Korea through the National Research Laboratory for Free Radicals.

Keywords

8-hydroxydeoxyguanosine
COX-2
Free radicals
NADPH oxidase
Rac1
STATs
iNOS

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10.1016/j.freeradbiomed.2006.07.018

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Kim, H. S., Ye, S. K., Cho, I. H., Jung, J. E., Kim, D. H., Choi, S., Kim, Y. S., Park, C. G., Kim, T. Y., Lee, J. W., & Chung, M. H. (2006). 8-hydroxydeoxyguanosine suppresses NO production and COX-2 activity via Rac1/STATs signaling in LPS-induced brain microglia. Free Radical Biology and Medicine, 41(9), 1392-1403. https://doi.org/10.1016/j.freeradbiomed.2006.07.018

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

abstract = "Free 8-hydroxydeoxyguanosine (oh8dG), a nucleoside of 8-hydroxyguanine (oh8Gua), 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 oh8dG inhibits lipopolysaccharide (LPS)-induced nitric oxide (NO) production and cyclooxygenase-2 (COX-2) activity, and both gene transcriptions in microglia. Furthermore, oh8dG reduced mRNA levels of pro-inflammatory cytokine, such as IL-1β, IL-6, and TNF-α, in activated BV2 cells. We also found that oh8dG suppressed reactive oxygen species (ROS) production through reduction of NADPH oxidase activity and blocked Rac1/STATs signal cascade. Finally, oh8dG 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 oh8dG as an anti-inflammatory agent.",

keywords = "8-hydroxydeoxyguanosine, COX-2, Free radicals, NADPH oxidase, Rac1, STATs, iNOS",

author = "Kim, \{Hong Sook\} and Ye, \{Sang Kyu\} and Cho, \{Ik Hyun\} and Jung, \{Joo Eun\} and Kim, \{Dong Hyun\} and Seongwon Choi and Kim, \{Yong Sik\} and Park, \{Chung Gyu\} and Kim, \{Tae Yoon\} and Lee, \{Jung Weon\} and Chung, \{Myung Hee\}",

note = "Funding Information: This study was supported by a grant of the Korea Health 21 R and D Project, Ministry of Health and Welfare (Project No.: A040004), and the Ministry of Science and Technology of Korea through the National Research Laboratory for Free Radicals.",

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AU - Kim, Hong Sook

AU - Ye, Sang Kyu

AU - Cho, Ik Hyun

AU - Jung, Joo Eun

AU - Kim, Dong Hyun

AU - Choi, Seongwon

AU - Kim, Yong Sik

AU - Park, Chung Gyu

AU - Kim, Tae Yoon

AU - Lee, Jung Weon

AU - Chung, Myung Hee

N1 - Funding Information: This study was supported by a grant of the Korea Health 21 R and D Project, Ministry of Health and Welfare (Project No.: A040004), and the Ministry of Science and Technology of Korea through the National Research Laboratory for Free Radicals.

PY - 2006/11/1

Y1 - 2006/11/1

N2 - Free 8-hydroxydeoxyguanosine (oh8dG), a nucleoside of 8-hydroxyguanine (oh8Gua), 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 oh8dG inhibits lipopolysaccharide (LPS)-induced nitric oxide (NO) production and cyclooxygenase-2 (COX-2) activity, and both gene transcriptions in microglia. Furthermore, oh8dG reduced mRNA levels of pro-inflammatory cytokine, such as IL-1β, IL-6, and TNF-α, in activated BV2 cells. We also found that oh8dG suppressed reactive oxygen species (ROS) production through reduction of NADPH oxidase activity and blocked Rac1/STATs signal cascade. Finally, oh8dG 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 oh8dG as an anti-inflammatory agent.

AB - Free 8-hydroxydeoxyguanosine (oh8dG), a nucleoside of 8-hydroxyguanine (oh8Gua), 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 oh8dG inhibits lipopolysaccharide (LPS)-induced nitric oxide (NO) production and cyclooxygenase-2 (COX-2) activity, and both gene transcriptions in microglia. Furthermore, oh8dG reduced mRNA levels of pro-inflammatory cytokine, such as IL-1β, IL-6, and TNF-α, in activated BV2 cells. We also found that oh8dG suppressed reactive oxygen species (ROS) production through reduction of NADPH oxidase activity and blocked Rac1/STATs signal cascade. Finally, oh8dG 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 oh8dG as an anti-inflammatory agent.

KW - 8-hydroxydeoxyguanosine

KW - COX-2

KW - Free radicals

KW - NADPH oxidase

KW - Rac1

KW - STATs

KW - iNOS

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ER -

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

Abstract

Bibliographical note

Keywords

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