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
- 주제(키워드) zearalenone , eNOS , PXR , Sp1 , NO
- 주제(기타) Food Science & Technology
- 주제(기타) Toxicology
- 설명문(일반) [Lee, Hyeon-Ju; Park, Jung-Hyun; Oh, Se-Young; Jo, Inho] Ewha Womans Univ, Coll Med, Dept Mol Med, Seoul 07804, South Korea; [Cho, Du-Hyong; Kim, Suji] Yeungnam Univ, Coll Med, Dept Pharmacol, 170 Hyunchung Ro, Daegu 42415, South Korea
- 등재 SCIE, SCOPUS
- OA유형 Green Published
- 발행기관 MDPI
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000172385
- 본문언어 영어
- Published As https://dx.doi.org/10.3390/toxins12060421
- PubMed https://pubmed.ncbi.nlm.nih.gov/32630586
초록/요약
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.
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