吡咯烷二硫代氨基甲酸酯
血红素加氧酶
蛋白激酶B
活性氧
PI3K/AKT/mTOR通路
LY294002型
信号转导
磷酸化
化学
NF-κB
MG132型
细胞生物学
血红素
αBκ
分子生物学
生物
生物化学
蛋白酶体抑制剂
细胞凋亡
酶
作者
Kyoung‐jin Min,Jung Tae Lee,Eun‐Hye Joe,Taeg Kyu Kwon
标识
DOI:10.1016/j.cellsig.2011.05.013
摘要
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.
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