ROS-induced ZNF580 expression: a key role for [H.sub.2][O.sub.2]/NF-κB signaling pathway in vascular endothelial inflammation

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 th...

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Bibliographic Details
Published in:Molecular and cellular biochemistry 2012-01, Vol.359 (1-2), p.183
Main Authors: DangLi, Ren, HeKong, Wang, JiQin, Liu, MingHua, Zhang, WenCheng, Zhang
Format: Article
Language:English
Subjects:
Endothelium
Enzyme-linked immunosorbent assay
Inflammation
Leukemia
Peroxides
Toy industry
Online Access:Get full text
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Summary: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 ([H.sub.2][O.sub.2])-regulated inflammation-related signaling pathways. In a human endothelial cell hybridoma line (EA.hy926), ZNF580 levels were markedly upregulated with [H.sub.2][O.sub.2] stimulation in different concentrations (0-400 µM) and at different time-points (0-6 h). [H.sub.2][O.sub.2] 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 [H.sub.2][O.sub.2].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 [H.sub.2][O.sub.2] 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. Keywords ZNF580 * [H.sub.2][O.sub.2] * NF-κB * Inflammation * IL-8
ISSN:0300-8177
1573-4919
DOI:10.1007/s11010-011-1013-0