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Zearalenone-Induced Interaction between PXR and Sp1 Increases Binding of Sp1 to a Promoter Site of the eNOS, Decreasing Its Transcription and NO Production in BAECs

Title
Zearalenone-Induced Interaction between PXR and Sp1 Increases Binding of Sp1 to a Promoter Site of the eNOS, Decreasing Its Transcription and NO Production in BAECs
Authors
Lee, Hyeon-JuPark, Jung-HyunOh, Se-YoungCho, Du-HyongKim, SujiJo, Inho
Ewha Authors
조인호오세영박정현
SCOPUS Author ID
조인호scopus
Issue Date
2020
Journal Title
TOXINS
ISSN
2072-6651JCR Link
Citation
TOXINS vol. 12, no. 6
Keywords
zearalenoneeNOSPXRSp1NO
Publisher
MDPI
Indexed
SCIE; SCOPUS WOS
Document Type
Article
Abstract
Zearalenone (ZEN) is a non-steroidal mycotoxin that has various toxicological impacts on mammalian health. Here, we found that ZEN significantly affected the production of nitric oxide (NO) and the expression of endothelial NO synthase (eNOS) of bovine aortic endothelial cells (BAECs). A promoter analysis using 5 '-serially deleted human eNOS promoter revealed that the proximal region (-135 to +22) was responsible for ZEN-mediated reduction of the human eNOS promoter activity. This effect was reversed by mutation of two specificity protein 1 (Sp1) binding elements in the human eNOS promoter. A chromatin immunoprecipitation assay revealed that ZEN increased Sp1 binding to the bovine eNOS promoter region (-113 to -12), which is homologous to -135 to +22 of the human eNOS promoter region. We also found that ZEN promoted the binding of the pregnane X receptor (PXR) to Sp1 of the bovine eNOS, consequently decreasing eNOS expression. This reduction of eNOS could have contributed to the decreased acetylcholine-induced vessel relaxation upon ZEN treatment in our ex vivo study using mouse aortas. In conclusion, our data demonstrate that ZEN decreases eNOS expression by enhancing the binding of PXR-Sp1 to the eNOS promoter, thereby decreasing NO production and potentially causing vessel dysfunction.
DOI
10.3390/toxins12060421
Appears in Collections:
의과대학 > 의학과 > Journal papers
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