1. ROS-induced ZNF580 expression: a key role for H2O2/NF-κB signaling pathway in vascular endothelial inflammation
- Author
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Wang HeKong, Ren Dang-li, Zhang MingHua, Zhang Wen-cheng, and Liu JiQin
- Subjects
Endothelium ,medicine.medical_treatment ,Clinical Biochemistry ,Biology ,chemistry.chemical_compound ,Pyrrolidine dithiocarbamate ,Cell Line, Tumor ,medicine ,Humans ,Molecular Biology ,Transcription factor ,chemistry.chemical_classification ,Inflammation ,Reactive oxygen species ,Interleukin-8 ,NF-kappa B ,NF-κB ,Cell Biology ,General Medicine ,Hydrogen Peroxide ,Molecular biology ,Cell biology ,Up-Regulation ,Endothelial stem cell ,medicine.anatomical_structure ,Cytokine ,chemistry ,Endothelium, Vascular ,Signal transduction ,Reactive Oxygen Species ,Signal Transduction ,Transcription Factors - Abstract
ZNF580, a newly found C2H2 zinc finger transcription factor, was first described by Zhang (GenBank ID: AF184939). Emerging evidence has suggested that reactive oxygen species (ROS) play an important role in redox-sensitive signal transduction, and the vascular endothelium plays a critical role in the vascular inflammatory response. In this communication, we present evidence for the potential role of ZNF580 in hydrogen peroxide (H2O2)-regulated inflammation-related signaling pathways. In a human endothelial cell hybridoma line (EA.hy926), ZNF580 levels were markedly upregulated with H2O2 stimulation in different concentrations (0–400 μM) and at different time-points (0–6 h). H2O2 promoted the rapid translocation of p65 from the cytoplasm into the nucleus according to immunocytochemistry staining. In subsequent research, inhibition of NF-κB by pyrrolidine dithiocarbamate (PDTC, a selective chemical inhibitor of NF-κB) was shown to block the upregulated expression of ZNF580 that was induced by H2O2. Furthermore, transient transfection of ZNF580 resulted in an increase of the pro-inflammatory cytokine interleukin-8 (IL-8) 3.01 ± 0.05 folds according to real-time RT-PCR and ELISA assays, which also showed significantly enhanced motility of human acute monocytic leukemia cells (THP-1). These results suggest that H2O2 upregulates the expression of ZNF580 via the NF-κB signaling pathway, and overexpression of ZNF580 plays a critical role in augmenting the release of pro-inflammatory cytokine IL-8.
- Published
- 2011