Oxidative stress enhances AP-1 and NF-κB-mediated regulation of β(2)-glycoprotein I gene expression in hepatoma cells.

β(2)-Glycoprotein I (β(2)-GPI), also known as apolipoprotein H, is a plasma glycoprotein with poorly defined gene regulation. The aim of this study was to clarify the role of oxidative stress in β(2)-GPI gene regulation and determine the essential transcription element regulating β(2)-GPI expression. We demonstrate that expression of β(2)-GPI at the protein and mRNA levels was significantly elevated in Huh7 and HepG2 cells treated with 100 µM hydrogen peroxide (H(2)O(2)). To address the transcriptional mechanism of H(2)O(2)-mediated β(2)-GPI gene regulation, several promoter constructs were cloned and characterized by deletion assays. A region spanning from -2141 to -1419 (relative to the transcription start site), which contains two activator protein-1 (AP-1) sites (AP1-2 and AP1-3) and one nuclear factor-kappaB (NF-κB) site was found to be the main target site for up-regulation of β(2)-GPI promoter activity by oxidative stress. In addition, we found that H(2)O(2) stimulation enhanced the nuclear translocation of AP-1 and NF-κB subunits. Using an electrophoretic mobility shift assay, it was confirmed that nuclear protein binding to the AP1-2, AP1-3, and NF-κB sites was increased in Huh7 cells treated with H(2)O(2). Knockdown of the c-Jun, c-Fos, p65, and p50 genes using small interfering RNAs (siRNAs) further confirmed that AP-1 and NF-κB play an essential role in the H(2)O(2)-induced β(2)-GPI expression. Overall, these findings provide new insight suggesting that multiple cis-elements in the β(2)-GPI promoter work cooperatively to regulate β(2)-GPI expression in cells under oxidative stress.

Chiu WC ，Chen CJ ，Lee TS ，Chen ZJ ，Ke PH ，Chiang AN ... -  《-》

Cloning and characterization of the human beta2-glycoprotein I (beta2-GPI) gene promoter: roles of the atypical TATA box and hepatic nuclear factor-1alpha in regulating beta2-GPI promoter activity.

Wang HH ，Chiang AN 《-》

Acetaldehyde induces matrix metalloproteinase-9 gene expression via nuclear factor-kappaB and activator protein 1 signaling pathways in human hepatocellular carcinoma cells: Association with the invasive potential.

Hsiang CY ，Wu SL ，Chen JC ，Lo HY ，Li CC ，Chiang SY ，Wu HC ，Ho TY ... -  《TOXICOLOGY LETTERS》

Constitutive activation of nuclear factor kappaB p50/p65 and Fra-1 and JunD is essential for deregulated interleukin 6 expression in prostate cancer.

Zerbini LF ，Wang Y ，Cho JY ，Libermann TA ... -  《CANCER RESEARCH》

Glucose depletion enhances P-glycoprotein expression in hepatoma cells: role of endoplasmic reticulum stress response.

Ledoux S ，Yang R ，Friedlander G ，Laouari D ... -  《CANCER RESEARCH》