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Expression of cytochrome P-450 4 enzymes in the kidney and liver: Regulation by PPAR and species-difference between rat and human

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Abstract

Members of the cytochrome P-450 4 (CYP4) family catalyze the ω-hydroxylation of fatty acids, and some of them have the PPAR response element in the promoter area of the genes. The localization of CYP4A and PPAR isoforms and the effect of PPAR agonists on CYP4A protein level and activity were determined in rat kidney and liver. Immunoblot analysis showed that CYP4A was expressed in the liver and proximal tubule, with lower expression in the preglomerular microvessel, glomerulus and thick ascending limb (TAL), but the expression was not detected in the collecting duct. PPARα was expressed in the liver, proximal tubule and TAL. PPARγ was expressed in the collecting duct, with lower expression in the TAL, but no expression in the proximal tubule and liver. The PPARα agonist clofibrate induced CYP4A protein levels and activity in the renal cortex and liver. The PPARγ agonist pioglitazone did not modulate them in these tissues. The localization of CYP4A and CYP4F were further determined in human kidney and liver by immunohistochemical technique. Immunostainings for CYP4A and CYP4F were observed in the hepatocytes of the liver lobule and the proximal tubules, with lower stainings in the TALs and collecting ducts, but no staining in the glomeruli or renal vasculatures. These results indicate that the inducibility of CYP4A by PPAR agonists in the rat tissues correlates with the expression of the respective PPAR isoforms, and that the localization of CYP4 in the kidney has a species-difference between rat and human.

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Authors and Affiliations

  1. Department of Internal Medicine and Rehabilitation Science,, Tohoku University Graduate School of Medicine, Sendai, Japan

    Osamu Ito, Liping Tan, Yuko Sasaki, Naoyoshi Minami, Masayuki Kanazawa & Masahiro Kohzuki

  2. Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan

    Yasuhiro Nakamura & Hironobu Sasano

  3. Department of Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan

    Tsuneo Ishizuka & Sadayoshi Ito

  4. Department of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine, Seiryo-machi 1-1, Sendai, 980-8574, Japan

    Osamu Ito

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  1. Osamu Ito
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  2. Yasuhiro Nakamura
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Ito, O., Nakamura, Y., Tan, L. et al. Expression of cytochrome P-450 4 enzymes in the kidney and liver: Regulation by PPAR and species-difference between rat and human. Mol Cell Biochem 284, 141–148 (2006). https://doi.org/10.1007/s11010-005-9038-x

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  • DOI: https://doi.org/10.1007/s11010-005-9038-x

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