title: Redox regulation of lipopolysaccharide-mediated sulfiredoxin induction, which depends on both AP-1 and Nrf2.
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.
authors.affiliation: Department of Life Science, Division of Life and Pharmaceutical Sciences, Center for Cell Signaling and Drug Discovery Research, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Hojin
authors.initials: H
authors.lastname: Kim
authors.forename: Yuyeon
authors.initials: Y
authors.lastname: Jung
authors.forename: Bong Soo
authors.initials: BS
authors.lastname: Shin
authors.forename: Hyeryeon
authors.initials: H
authors.lastname: Kim
authors.forename: Hyunsook
authors.initials: H
authors.lastname: Song
authors.forename: Soo Han
authors.initials: SH
authors.lastname: Bae
authors.forename: Sue Goo
authors.initials: SG
authors.lastname: Rhee
authors.forename: Woojin
authors.initials: W
authors.lastname: Jeong
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D002384:Catalysis; D002460:Cell Line; D003545:Cysteine / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D016166:Free Radical Scavengers; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009861:Onium Compounds / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000096:biosynthesis* / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D020218:Response Elements; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; D009861:Onium Compounds; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D002083:Butylated Hydroxyanisole; C007517:diphenyleneiodonium; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D050862:Oxidoreductases Acting on Sulfur Group Donors; C529381:sulfiredoxin protein, mouse; D003545:Cysteine; C013461:cysteine sulfinic acid; D000111:Acetylcysteine
references.citation: J Biol Chem. 2002 Jun 21;277(25):22131-9
references.pmid: 11940570
references.citation: J Biol Chem. 2005 Feb 4;280(5):3125-8
references.pmid: 15590625
references.citation: J Immunol. 2005 Oct 1;175(7):4408-15
references.pmid: 16177082
references.citation: Free Radic Biol Med. 2009 Feb 1;46(3):376-86
references.pmid: 19027064
references.citation: Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11908-13
references.pmid: 12193649
references.citation: J Biol Chem. 2008 Aug 15;283(33):22371-82
references.pmid: 18552404
references.citation: J Biol Chem. 2002 May 31;277(22):19396-401
references.pmid: 11904290
references.citation: FASEB J. 1999 Jul;13(10):1169-83
references.pmid: 10385608
references.citation: J Immunol. 2004 Feb 15;172(4):2522-9
references.pmid: 14764725
references.citation: Semin Immunol. 2007 Feb;19(1):24-32
references.pmid: 17275323
references.citation: J Biol Chem. 2008 Aug 29;283(35):23846-51
references.pmid: 18579529
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19738-43
references.pmid: 19057013
references.citation: Cell. 1995 Jun 30;81(7):1137-46
references.pmid: 7600581
references.citation: J Biol Chem. 2003 Nov 28;278(48):47361-4
references.pmid: 14559909
references.citation: J Cell Physiol. 2002 Apr;191(1):95-104
references.pmid: 11920685
references.citation: IUBMB Life. 2001 Jul;52(1-2):35-41
references.pmid: 11795591
references.citation: Biochem J. 2001 Jul 15;357(Pt 2):447-55
references.pmid: 11439094
references.citation: J Biol Chem. 1998 Jun 19;273(25):15366-72
references.pmid: 9624118
references.citation: N Engl J Med. 1997 Apr 10;336(15):1066-71
references.pmid: 9091804
references.citation: EMBO J. 1998 May 1;17(9):2596-606
references.pmid: 9564042
references.citation: Int J Hematol. 2006 Oct;84(3):193-8
references.pmid: 17050190
references.citation: Biochem Biophys Res Commun. 1997 Jul 18;236(2):313-22
references.pmid: 9240432
references.citation: J Biol Chem. 2009 Aug 28;284(35):23364-74
references.pmid: 19561357
references.citation: EMBO J. 1992 Feb;11(2):653-65
references.pmid: 1537340
references.citation: J Biol Chem. 2009 Mar 27;284(13):8470-7
references.pmid: 19176523
references.citation: J Biol Chem. 1998 Jul 10;273(28):17477-82
references.pmid: 9651337
references.citation: J Biol Chem. 2002 Oct 11;277(41):38029-36
references.pmid: 12161445
references.citation: Antioxid Redox Signal. 2005 May-Jun;7(5-6):768-77
references.pmid: 15890023
references.citation: Adv Cancer Res. 1995;66:255-92
references.pmid: 7793317
references.citation: Biochim Biophys Acta. 2010 May-Jun;1799(5-6):402-10
references.pmid: 19941984
references.citation: J Biol Chem. 2002 Sep 20;277(38):35232-9
references.pmid: 12093805
references.citation: J Biol Chem. 2004 Dec 3;279(49):50994-1001
references.pmid: 15448164
references.citation: J Biol Chem. 2002 Nov 8;277(45):42769-74
references.pmid: 12198130
references.citation: Biochem J. 2003 Sep 1;374(Pt 2):337-48
references.pmid: 12816537
references.citation: J Immunol. 2008 Nov 15;181(10):6730-7
references.pmid: 18981090
references.citation: Mol Cell Biol. 2005 Jul;25(14):5933-46
references.pmid: 15988009
references.citation: J Exp Med. 2007 Mar 19;204(3):583-94
references.pmid: 17325201
references.citation: BMC Mol Biol. 2007 Jun 22;8:54
references.pmid: 17587450
references.citation: Trends Microbiol. 2004 Apr;12(4):186-92
references.pmid: 15051069
references.citation: Am J Respir Crit Care Med. 2002 Dec 15;166(12 Pt 2):S4-8
references.pmid: 12471082
references.citation: J Biol Chem. 2004 Dec 10;279(50):51715-8
references.pmid: 15364933
references.citation: J Biol Chem. 2006 May 19;281(20):14400-7
references.pmid: 16565085
references.citation: Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):2040-5
references.pmid: 14764894
references.citation: Science. 1990 Sep 7;249(4973):1157-61
references.pmid: 2118682
references.citation: Cancer Res. 2006 Jul 1;66(13):6800-6
references.pmid: 16818657
references.citation: J Neurochem. 2008 Oct;107(2):533-43
references.pmid: 18761713
references.citation: Science. 2003 Apr 25;300(5619):653-6
references.pmid: 12714748
references.citation: Nature. 2003 Oct 30;425(6961):980-4
references.pmid: 14586471
references.citation: Nat Immunol. 2005 Jun;6(6):587-92
references.pmid: 15864310
references.citation: Kidney Int Suppl. 2007 Aug;(106):S3-8
references.pmid: 17653208
references.citation: Curr Opin Cell Biol. 2005 Apr;17(2):183-9
references.pmid: 15780595
references.citation: Antioxid Redox Signal. 2009 May;11(5):937-48
references.pmid: 19086807
references.citation: Biochim Biophys Acta. 2004 Jun 28;1657(1):1-22
references.pmid: 15238208
references.citation: Cell. 2006 Feb 24;124(4):783-801
references.pmid: 16497588
references.citation: Genes Dev. 1999 Jan 1;13(1):76-86
references.pmid: 9887101
references.citation: Blood. 2005 Aug 1;106(3):852-9
references.pmid: 15817678
references.citation: Cell. 2005 Mar 11;120(5):649-61
references.pmid: 15766528
references.citation: Mol Cell Biol. 2003 Jul;23(13):4673-86
references.pmid: 12808106
references.citation: J Biol Chem. 1997 Mar 14;272(11):7445-54
references.pmid: 9054446
references.citation: J Biol Chem. 2000 Dec 29;275(52):41035-48
references.pmid: 10969071
references.citation: J Biol Chem. 1999 Nov 19;274(47):33627-36
references.pmid: 10559251
references.citation: Proc Natl Acad Sci U S A. 1997 May 13;94(10):5361-6
references.pmid: 9144242
references.citation: Semin Immunol. 2004 Feb;16(1):3-9
references.pmid: 14751757
references.citation: J Biol Chem. 2001 Aug 10;276(32):30188-98
references.pmid: 11402028
references.citation: Annu Rev Immunol. 1995;13:437-57
references.pmid: 7542010
references.citation: Nat Neurosci. 2008 Apr;11(4):476-87
references.pmid: 18344994
references.citation: Mol Cells. 2009 Mar 31;27(3):279-82
references.pmid: 19326073
references.citation: J Biol Chem. 1995 Nov 24;270(47):27995-8
references.pmid: 7499279
references.citation: J Biochem. 2009 Apr;145(4):425-7
references.pmid: 19155266
references.citation: Free Radic Biol Med. 2009 Sep 15;47(6):794-802
references.pmid: 19540914
references.citation: J Biol Chem. 1992 Jul 25;267(21):15097-104
references.pmid: 1340765
references.citation: J Biol Chem. 1998 Jun 12;273(24):14683-9
references.pmid: 9614065
references.citation: Mol Cell. 2002 Feb;9(2):387-99
references.pmid: 11864611
references.citation: Nat Rev Immunol. 2004 Mar;4(3):181-9
references.pmid: 15039755
references.citation: Biochem Biophys Res Commun. 2000 Nov 19;278(2):484-92
references.pmid: 11097862
references.citation: Cell. 2000 Oct 13;103(2):239-52
references.pmid: 11057897
references.citation: Gene. 2002 Jul 10;294(1-2):1-12
references.pmid: 12234662
references.citation: Biochem Biophys Res Commun. 2007 Apr 13;355(3):715-21
references.pmid: 17316558
references.citation: Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4611-6
references.pmid: 11287661
references.citation: Am J Physiol Lung Cell Mol Physiol. 2000 Dec;279(6):L1005-28
references.pmid: 11076791