| Project/Area Number |
15390040
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental pharmacy
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
YAMAZAKI Hiroshi Hokkaido Univ., Grad.School of Pharm.Sci., Asso.Prof., 大学院・薬学研究科, 助教授 (30191274)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIEDA Masaki Hokkaido Univ., Grad.School of Pharm.Sci., Inst., 大学院・薬学研究科, 助手 (00344474)
KAMATAKI Tetsuya Hokkaido Univ., Grad.School of Pharm.Sci., Prof., 大学院・薬学研究科, 教授 (00009177)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2004: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2003: ¥9,700,000 (Direct Cost: ¥9,700,000)
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| Keywords | AHR / PAHs / TCDD / CYP1A1 / CYP1B1 / 個人差 |
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| Research Abstract |
Polycychc aromatic hydrocarbons (PAHs) which are known as the Environmental Endocrine Disruptors exert the various toxicological effects via aryl hydrocarbon receptor (AHR). However the mechanisms of toxic expression induced by PAHs have not been clarified yet. Therefore, the purpose of this study was to clarify the mechanisms of toxic expression induced by PAHs using differential display method and DNA microarray method. First, total RNA were prepared from the wild type mouse and AHR knock out mouse livers treated. with 3-methylcholanthrene (MC). We found the novel AHR target genes using differential display method and DNA microarray method. Interestingly, the mRNA expressions of the peroxisome prolifilator-activated receptor (PPAR) α target genes were suppressed by PAH treatment through AHR. We also demonstrated that AHR inhibited PPARα signals through the suppression of its heterodimeric partner, retinoid X receptor (RXR)α. The genes responsible for the fatty acid metabolism were regulated by PPARα. Therefore, it was suggested that the suppression of the PPARα signal was important for the occurrence of fatty liver.
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