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2000 Fiscal Year Final Research Report Summary

Molecular mechanism (s) responsible for species difference in dioxin toxicity

Research Project

Project/Area Number 11672225
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental pharmacy
Research InstitutionHokkaido University

Principal Investigator

TAKAHASHI Yoshiki  Hokkaido University Pharmaceutical Sciences Instructor, 大学院・薬学研究科, 助手 (80292019)

Co-Investigator(Kenkyū-buntansha) ARIYOSHI Noritaka  Hokkaido University Pharmaceutical Sciences Associate Professor, 大学院・薬学研究科, 助教授 (00243957)
FUJITA Kenichi  Hokkaido University Pharmaceutical Sciences Instructor, 大学院・薬学研究科, 助手 (60281820)
Project Period (FY) 1999 – 2000
KeywordsAryl hydrocarbon / receptor / Xenobiotic-responsive element
Research Abstract

A xenobiotic-responsive element (XRE)-binding factor (s) other than aromatic hydrocarbon receptor (AhR)/AhR nuclear translocator (Arnt) complex was found to inhibit the transcription of the guinea pig NAD (P) H : quinone oxidoreductase_1 (NQO_1) gene. Within the 5'-flanking region up to -1.6 kilobase of this gene, there were two possible XREs, designated as XRE1 and XRE2. XRE1 but not XRE2 interacted with AhR/Arnt complex in vitro. Interestingly, the activation of 10xXRE1-Luc reporter gene with ten copies of XRE1 by AhR/Arnt complex was seen in Drosophila Schneider line 2 (SL2) cells but not in human hepatoblastoma HepG2 cells. A super shift assay using antibodies to AhR and nuclear extracts from HepG2 cells treated with 2, 3, 7, 8-tetrachlorodibenzofuran revealed that XRE1 bound to an unknown factor (s), which was distinct from AhR/Arnt complex. Searching the sequence similar to XRE1, the sequence of XRE1 overlapped with that of specificity protein 1 (Sp1)-binding site. Our super shift assay showed that the unknown factor (s) was identical to Sp1. Furthermore, the AhR/Arnt-mediated activation of the 10xXRE1-Luc in SL2 cells was blocked with the amount of Sp1 expression plasmid transfected. Thus, we conclude that Sp1 and AhR/Arnt complex bind to the XRE1 of the guinea pig NQO_1 gene in a mutually exclusive manner.

  • Research Products

    (1 results)

All Other

All Publications (1 results)

  • [Publications] Eri Inoue,Yoshiki Takahashi et al.: "Development of bacterial expression system with high yield of CYP3A7, a human fetus specific form of cytochrome P450."Biochem.Biophys.Res.Commun.. 269. 623-627

    • Description
      「研究成果報告書概要(和文)」より

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Published: 2002-03-26  

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