Microgram-order ammonium perfluorooctanoate may activate mouse peroxisome proliferator-activated receptor α, but not human PPARα

Toshiki Nakamura, Yuki Ito, Yukie Yanagiba, Doni Hikmat Ramdhan, Yasuhide Kono, Hisao Naito, Yumi Hayashi, Yufei Li, Toshifumi Aoyama, Frank J. Gonzalez, Tamie Nakajima

研究成果: Article

33 引用 (Scopus)

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Perfluorooctanoic acid (PFOA) is a ligand for peroxisome proliferator-activated receptor (PPAR) α, which exhibits marked species differences in expression and function, especially between rodents and humans. We investigated the functional difference in PFOA response between mice and humans, using a humanized PPARα transgenic mouse line. Three genotyped mice, 129/Sv wild-type (mPPARα), Pparα-null mice and humanized PPARα (hPPARα) mice (8-week-old males) were divided into three groups: the first was treated with water daily for 2 weeks by gavage (control group), and the remaining two groups were treated with 0.1 and 0.3 mg/kg ammonium perflurooctanate (APFO), respectively, for 2 weeks by gavage. The APFO dosages used did not influence the plasma triglyceride or total cholesterol levels in any mouse line, but the high dose increased both hepatic lipid levels only in mPPARα mice. APFO increased mRNA and/or protein levels of PPARα target genes cytochrome P450 Cyp4a10, peroxisomal thiolase and bifunctional protein only in the liver of mPPARα mice, but not in Pparα-null or hPPARα mice. This chemical also increased expression of mitochondrial very long chain acyl-CoA dehydrogenase only in the liver of mPPARα mice. Taken together, human PPARα may be less responsive to PFOA than that of mice when a relatively low dose is applied. This information may be very valuable in considering whether PFOA influences the lipid metabolism in humans.

元の言語English
ページ(範囲)27-33
ページ数7
ジャーナルToxicology
265
発行部数1-2
DOI
出版物ステータスPublished - 09-11-2009

All Science Journal Classification (ASJC) codes

  • Toxicology

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    Nakamura, T., Ito, Y., Yanagiba, Y., Ramdhan, D. H., Kono, Y., Naito, H., Hayashi, Y., Li, Y., Aoyama, T., Gonzalez, F. J., & Nakajima, T. (2009). Microgram-order ammonium perfluorooctanoate may activate mouse peroxisome proliferator-activated receptor α, but not human PPARα. Toxicology, 265(1-2), 27-33. https://doi.org/10.1016/j.tox.2009.09.004