論文

査読有り
2007年7月

Dietary phytochemicals regulate wholebody CYP1A1 expression through an arylhydrocarbon receptor nuclear translocator-dependent system in gut

JOURNAL OF CLINICAL INVESTIGATION
  • Shinji Ito
  • ,
  • Chi Chen
  • ,
  • Junko Satoh
  • ,
  • SunHee Yim
  • ,
  • Frank J. Gonzalez

117
7
開始ページ
1940
終了ページ
1950
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1172/JCI31647
出版者・発行元
AMER SOC CLINICAL INVESTIGATION INC

Cytochrome P450 1A1 (CYP1A1) is one of the most important detoxification enzymes due to its broad substrate specificity and wide distribution throughout the body. On the other hand, CYP1A1 can also produce highly carcinogenic intermediate metabolites through oxidation of polycyclic aromatic hydrocarbons. We describe what we believe to be a novel regulatory system for whole-body CYP1A1 expression by a factor originating in the gut. A mutant mouse was generated in which the arylhydrocarbon receptor nuclear translocator (Arnt) gene is disrupted predominantly in the gut epithelium. Surprisingly, CYP1A1 mRNA expression and enzymatic activities were markedly elevated in almost all non-gut tissues in this mouse line. The induction was even observed in early-stage embryos in pregnant mutant females. Interestingly, the upregulation was CYP1A1 selective and lost upon administration of a synthetic purified diet. Moreover, the increase was recovered by addition of the natural phytochemical indole-3-carbinol to the purified diet. These results suggest that an Arnt-dependent pathway in gut has an important role in regulation of the metabolism of dietary CYP1A1 inducers and whole-body CYP1A1 expression. This machinery might be involved in naturally occurring carcinogenic processes and/or other numerous biological responses mediated by CYP1A1 activity.

Web of Science ® 被引用回数 : 65

リンク情報
DOI
https://doi.org/10.1172/JCI31647
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000247837700026&DestApp=WOS_CPL
ID情報
  • DOI : 10.1172/JCI31647
  • ISSN : 0021-9738
  • Web of Science ID : WOS:000247837700026

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