Down Regulation of Hepatic PPARα Function by AhR Ligand

• SHABAN Zein

  Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University Department of Biochemistry & Physiology, Faculty of Veterinary Medicine, Tanta University

• El-SHAZLY Samir

  Department of Biochemistry & Physiology, Faculty of Veterinary Medicine, Tanta University

• ABDELHADY Shawky

  Department of Biochemistry & Physiology, Faculty of Veterinary Medicine, Tanta University

• FATTOUH Ibrahim

  Department of Biochemistry & Physiology, Faculty of Veterinary Medicine, Tanta University

• MUZANDU Kaampwe

  Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University

• ISHIZUKA Mayumi

  Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University

• KIMURA Kazuhiro

  Laboratory of Biochemistry, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University

• KAZUSAKA Akio

  Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University

• FUJITA Shoichi

  Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University

書誌事項

タイトル別名

• Down Regulation of Hepatic PPAR.ALPHA. Function by AhR Ligand
• Down Regulation of Hepatic PPAR アルファ Function by AhR Ligand

抄録

Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates a spectrum of toxic and biological effects of 2,3,7,8-tetrachloro dibenzo-p-dioxin (TCDD) and related compounds. Peroxisome proliferator activated receptor alpha (PPARα) is a nuclear receptor involved in the maintenance of lipid and glucose homeostasis. In this study we hypothesized that one of the possible mechanisms for the effect of TCDD and its related chemicals on fat metabolism could be through down regulation of PPARα functions. We treated Wistar rats with an AhR ligand, Sudan III (S.III), and/or PPARα ligand, Clofibric Acid (CA), for 3 days. We analysed the expression of one of the PPARα-target gene products, CYP4A protein and its mRNA. We also tested HepG2 cells with the afore-mentioned treatments and evaluated their effects on PPARα and RXRα protein. Treatment of Wistar rats with S.III was found to down regulates CYP4A protein expression and reduced its induction with CA. It also decreased mRNA expressions of CYP4A1, CYP4A2, CYP4A3 and PPARα. In HepG2 cells, PPARα and RXRα protein expression was decreased by S.III treatment in a dose dependent manner. Our results suggest that AhR has an inhibitory effect on PPARα function and a new pathway by which AhR ligands could disturb lipid metabolism.<br>

収録刊行物

• Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｖｅｔｅｒｉｎａｒｙ　Ｍｅｄｉｃａｌ　Ｓｃｉｅｎｃｅ

  Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｖｅｔｅｒｉｎａｒｙ　Ｍｅｄｉｃａｌ　Ｓｃｉｅｎｃｅ 66 (11), 1377-1386, 2004

  公益社団法人 日本獣医学会

キーワード

• AhR
• CYP4A
• PPARα rat
• RXRα

詳細情報

• CRID: 1390001206424248704
• NII論文ID: 110003963618
• NII書誌ID: AA10796138
• DOI: 10.1292/jvms.66.1377
• ISSN: 13477439
• ISSN: 09167250
• NDL書誌ID: 7166103
• PubMed: 15585952
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I7166103
• Web Site: http://www.jstage.jst.go.jp/article/jvms/66/11/66_11_1377/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2005067724
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可