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

Authors
Kyoung-jin MinJung Tae LeeEun-hye JoeTaeg Kyu Kwon
Department
Dept. of Immunology (면역학)
Issue Date
2011
Citation
Cellular Signalling, Vol.23(9) : 1505-1513, 2011
ISSN
0898-6568
Abstract
Reactive 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. Keywords Bay 11-7082; Heme oxygenase-1; NF-κB; Reactive oxygen species; Nrf2; PI3K
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35387
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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Full Text
http://lps3.linkinghub.elsevier.com.proxy.dsmc.or.kr/retrieve/pii/S0898-6568(11)00150-1
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