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An IκBα phosphorylation inhibitor induces heme oxygenase-1(HO-1) expression through the activation of reactive oxygen species (ROS)-Nrf2-ARE signaling and ROS-PI3K/Akt signaling in an NF-κB-independent mechanism

DC Field Value Language
dc.contributor.authorMin, KJ-
dc.contributor.authorLee, JT-
dc.contributor.authorJoe, EH-
dc.contributor.authorKwon, TK-
dc.date.accessioned2012-03-29-
dc.date.available2012-03-29-
dc.date.issued2011-
dc.identifier.issn0898-6568-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/6352-
dc.description.abstractReactive oxygen species (ROS) are important signaling molecules in cells. Excessive ROS induce expression of inflammatory mediators, such as iNOS and COX2. Antioxidant enzymes, such as, heme oxygenase-1 (HO-1), tightly regulate ROS levels within cells. Here, we show that Bay 11-7082 (Bay) increased HO-1 mRNA and protein expression in human colon cancer HT29 cells. Bay induced translocation of NF-E2-related factor 2 (Nrf2) into nuclei and increased the binding activity of the antioxidant response element (ARE). In addition, PI3K/Akt inhibitor (LY294002) blocked Bay-induced HO-1 expression. Pretreatment with anti-oxidants (N-acetylcysteine (NAC) or glutathione) significantly reduced Bay-induced HO-1 mRNA/protein expression, nuclear translocation of Nrf2 and phosphorylation of Akt. However, PI3K/Akt signaling was independent of Bay-induced Nrf2 translocation and ARE binding activity. Furthermore, other NF-κB inhibitors, such as pyrrolidine dithiocarbamate (PDTC) and MG132, also increased HO-1 mRNA and protein expression. However, although overexpression of dominant negative inhibitory κB (IκB) reduced NF-κB-driven transcriptional activity, IκB overexpression did not increase HO-1 expression. Taken together, our results suggest that in human colon cancer HT29 cells, Bay induces HO-1 expression by increasing ROS production in an Nrf2-ARE and PI3K dependent manner, but Bay acts independently of NF-κB.-
dc.language.isoen-
dc.subject.MESHAnalysis of Variance-
dc.subject.MESHElectrophoretic Mobility Shift Assay-
dc.subject.MESHGene Expression Regulation-
dc.subject.MESHGlutathione/pharmacology-
dc.subject.MESHHT29 Cells-
dc.subject.MESHHeme Oxygenase-1/*metabolism-
dc.subject.MESHHumans-
dc.subject.MESHImmunohistochemistry-
dc.subject.MESHLeupeptins/pharmacology-
dc.subject.MESHNF-E2-Related Factor 2/metabolism-
dc.subject.MESHNF-kappa B/antagonists & inhibitors-
dc.subject.MESHNitriles/*pharmacology-
dc.subject.MESHPhosphatidylinositol 3-Kinases/metabolism-
dc.subject.MESHPhosphorylation-
dc.subject.MESHProline/analogs & derivatives/pharmacology-
dc.subject.MESHProto-Oncogene Proteins c-akt/metabolism-
dc.subject.MESHRNA, Messenger/metabolism-
dc.subject.MESHReactive Oxygen Species/*metabolism-
dc.subject.MESHResponse Elements-
dc.subject.MESH*Signal Transduction-
dc.subject.MESHSulfones/*pharmacology-
dc.subject.MESHThiocarbamates/pharmacology-
dc.subject.MESHTransfection-
dc.titleAn IκBα phosphorylation inhibitor induces heme oxygenase-1(HO-1) expression through the activation of reactive oxygen species (ROS)-Nrf2-ARE signaling and ROS-PI3K/Akt signaling in an NF-κB-independent mechanism-
dc.typeArticle-
dc.identifier.pmid21620964-
dc.identifier.urlhttp://linkinghub.elsevier.com/retrieve/pii/S0898-6568(11)00150-1-
dc.contributor.affiliatedAuthor조, 은혜-
dc.type.localJournal Papers-
dc.identifier.doi10.1016/j.cellsig.2011.05.013-
dc.citation.titleCellular signalling-
dc.citation.volume23-
dc.citation.number9-
dc.citation.date2011-
dc.citation.startPage1505-
dc.citation.endPage1513-
dc.identifier.bibliographicCitationCellular signalling, 23(9):1505-1513, 2011-
dc.identifier.eissn1873-3913-
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Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
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