title: ROS-induced ZNF580 expression: a key role for H2O2/NF-κB signaling pathway in vascular endothelial inflammation.
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.
authors.affiliation: Department of Clinical Laboratory, The Affiliated Hospital, Medical College of Chinese People's Armed Police Force, Tianjin, 300162, China. ren.dangli@163.com
authors.forename: Ren
authors.initials: R
authors.lastname: DangLi
authors.forename: Wang
authors.initials: W
authors.lastname: HeKong
authors.forename: Liu
authors.initials: L
authors.lastname: JiQin
authors.forename: Zhang
authors.initials: Z
authors.lastname: MingHua
authors.forename: Zhang
authors.initials: Z
authors.lastname: WenCheng
mesh_terms: D045744:Cell Line, Tumor; D004730:Endothelium, Vascular / Q000473:pathology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism*; D016209:Interleukin-8; D016328:NF-kappa B / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014157:Transcription Factors; C550122:ZNF580 protein, human; D006861:Hydrogen Peroxide