Increased catalytic activity of cytochrome P-450IIE1 in pericentral hepatocytes compared to periportal hepatocytes isolated from pyrazole-treated rats

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Abstract

Cytochrome P-450IIE1 is induced by a variety of agents, including acetone, ethanol and pyrazole. Recent studies employing immunohistochemical methods have shown that P-450IIE1 was expressed primarily in the pericentral zone of the liver. In order to evaluate whether catalytic activity of P-450IIE1 is preferentially localized in the pericentral zone of the liver acinus, the oxidation of aniline and p-nitrophenol, two effective substrates for P-450IIE1, by periportal and pericentral hepatocytes isolated from pyrazole-treated rats was determined. Periportal and pericentral hepatocytes were prepared by a digitonin-collagenase procedure; the marker enzymes glutamine synthetase and γ-glutamyl transpeptidase indicated reasonable separation of the two cell populations. Viability, yield and total cytochrome P-450 content were similar to the periportal and pericentral hepatocytes. Pericentral hepatocytes oxidized aniline and p-nitrophenol at rates that were 2–4-fold greater than periportal hepatocytes under a variety of conditions. Carbon monoxide inhibited the oxidation of the substrates with both preparations and abolished the increased oxidation found with the pericentral hepatocytes. Pyrazole or 4-methylpyrzaole, added in vitro, effectively inhibited the oxidation of aniline and p-nitrophenol and prevented the augmented rate of oxidation by the pericentral hepatocytes. Western blots carried out using isolated microsomes revealed a more than 2-fold increase in immunochemical staining with microsomes isolated from the pericentral hepatocytes, which correlated to the 2–4-fold increase in the rate of oxidation of aniline or p-nitrophenol by the pericentral hepatocytes. These results suggest that functional catalytic activity of cytochrome P-450IIE1 is preferentially localized in the pericentral zone of the liver acinus, and that most of the induction by pyrazole of P-450IIE1 appears to occur within the pericentral zone.

Reference (67)

  • MorganE.T. et al.

    J. Biol. Chem.

    (1982)
  • KoopD.R. et al.

    J. Biol. Chem.

    (1982)
  • RyanD.E. et al.

    Arch. Biochem. Biophys.

    (1986)
  • KoopD.R. et al.

    J. Biol. Chem.

    (1985)
  • PattenC.J. et al.

    Arch. Biochem. Biophys.

    (1986)
  • RyanD.E. et al.

    J. Biol. Chem.

    (1985)
  • TuY.Y. et al.

    Biochem. Biophys. Res. Commun.

    (1981)
  • Ingelman-SundbergM. et al.

    Biochem. Biophys. Res. Commun.

    (1984)
  • PowisG. et al.

    Biochem. Pharmacol.

    (1976)
  • YangC.S. et al.

    Biochem. Biophys. Res. Commun.

    (1985)
  • KrikunG. et al.

    Biochim. Biophys. Acta

    (1984)
  • MorganE.T. et al.

    Biochem. Biophys. Res. Commun.

    (1983)
  • JohanssonI. et al.

    FEBS Lett.

    (1985)
  • KoopD.R. et al.

    Toxicol. Appl. Pharmacol.

    (1989)
  • GoodingP.E. et al.

    Chem.-Biol. Interact.

    (1978)
  • SmithM.T. et al.

    FEBS Lett.

    (1981)
  • BaronJ. et al.

    J. Biol. Chem.

    (1981)
  • BaronJ. et al.

    J. Biol. Chem.

    (1982)
  • Ingelman-SundbergM. et al.

    Biochem. Biophys. Res. Commun.

    (1988)
  • HongJ. et al.

    Biochem. Biophys. Res. Commun.

    (1987)
  • MieyalJ.J. et al.

    J. Biol. Chem.

    (1976)
  • OmuraT. et al.

    J. Biol. Chem.

    (1964)
  • LindrosK.O. et al.

    J. Hepatology

    (1989)
  • DickerE. et al.

    Biochim. Biophys. Acta

    (1990)
  • RubinE. et al.

    Biochem. Biophys. Res. Commun.

    (1971)
  • FeiermanD.E. et al.

    Biochem. Biophys. Res. Commun.

    (1985)
  • FeiermanD.E. et al.

    Biochem. Pharmacol.

    (1987)
  • DeGrootC.J. et al.

    Biochim. Biophys. Acta

    (1987)
  • SuolinnaE. et al.

    Biochem. Pharmacol.

    (1989)
  • ReinkeL.A. et al.

    Biochem. Pharmacol.

    (1980)
  • ThomasP.E. et al.

    Biochemistry

    (1987)
  • KimS.D. et al.

    J. Pharmacol. Exp. Ther.

    (1988)
  • KoopD.R. et al.
  • Cited by (0)

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