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Redox regulation of lipopolysaccharide-mediated sulfiredoxin induction, which depends on both AP-1 and Nrf2

Title
Redox regulation of lipopolysaccharide-mediated sulfiredoxin induction, which depends on both AP-1 and Nrf2
Authors
Kim H.Jung Y.Shin B.S.Song H.Bae S.H.Rhee S.G.Jeong W.
Ewha Authors
이서구정우진배수한
SCOPUS Author ID
이서구scopusscopus; 정우진scopus
Issue Date
2010
Journal Title
Journal of Biological Chemistry
ISSN
0021-9258JCR Link
Citation
vol. 285, no. 45, pp. 34419 - 34428
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Sulfiredoxin (Srx) is an enzyme that catalyzes the reduction of cysteine sulfinic acid of hyperoxidized peroxiredoxins and exerts a protective antioxidant role. Here we investigated the regulatory mechanism of Srx induction by lipopolysaccharide (LPS) in mouse macrophages. LPS up-regulated Srx expression on the transcriptional level. The promoter region of the Srx gene contained putative NF-κB and AP-1 (activator protein-1) sites, and the proximal site of three AP-1 sites was embedded within the antioxidant response element (ARE), a cis-acting element for Nrf2 (nuclear factor erythroid 2-related factor). Mutational analysis of the Srx promoter revealed that Srx induction is dependent on AP-1 sites and ARE but not on NF-κB sites. Consistently, both transcription factors, AP-1 and Nrf2, were required for LPS-mediated Srx induction, as revealed by chromatin immunoprecipitation using antibodies specific for c-Jun and c-Fos and little Srx induction in Nrf2-null bone marrow-derived macrophages. Among mitogen-activated protein kinases that mediate the signal transduction by LPS, JNK played a major role in Srx induction. Moreover, chemical antioxidants, such as N-acetylcysteine and butylated hydroxyanisole, and the NADPH oxidase inhibitor diphenyleneiodonium inhibited Srx induction as well as generation of reactive oxygen species, both of which were also suppressed in Nox2 (NADPH oxidase 2)-deficient bone marrow-derived macrophages. These results suggest that LPS-mediated Srx induction is dependent on both AP-1 and Nrf2, which is regulated by Nox2-derived reactive oxygen species. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
DOI
10.1074/jbc.M110.126839
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일반대학원 > 생명·약학부 > Journal papers
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