Changes in the amount of cytochrome P450s in rat hepatic microsomes with starvation

https://doi.org/10.1016/0003-9861(90)90245-TGet rights and content

Abstract

The effects of starvation on the composition of 12 different cytochrome P450s in rat hepatic microsomes were studied with a specific antibody. Changes in the metabolic activity of the microsomes were studied at the same time. P450 DM (P450j) was induced 2.5-fold by a 48-h starvation and its increase reflected the increase of metabolic activity of hepatic microsomes toward aniline, 7-ethoxycoumarin, and N-nitrosodimethylamine. P450 K-5, the major renal cytochrome P450 in untreated male rat, was also induced 2.5-fold by a 48-h starvation. P450 UT-2 (P450h) and P450 UT-5 (P450g), typical male-specific forms, decreased with starvation. P450 UT-2 had high testosterone 2α-and 16α-hydroxylation activities. These activities of hepatic microsomes were reduced with the decrease in P450 UT-2. P450 PB-1, testosterone 6β-hydroxylase, was increased time-dependently by starvation. P450 UT-4 (RLM2), a minor male-specific form, was not changed by starvation. P450 PB-2 (P450k), present in both sexes, was changed little by starvation. P450 PB4 (P450b) and P450 PB-5 (P450e) are strongly induced in rat liver by phenobarbital in coordinate fashion. Starvation increased P45O PB-4 12-fold but reduced P450 PB-5 to 22% of the control level. P450 MC-1 (P450d) was decreased by starvation. P450 MC-5 (P450c) was barely detected in control rats and was not changed by starvation. P450 IF-3 (P450a), rich in immature rats, was increased by starvation, accompanied by an increase in testosterone 7α-hydroxylation activity in the hepatic microsomes. We further investigated whether new cytochrome P450s appeared upon starvation by comparison of Chromatographic profiles of cytochrome P450 from starved rats with those of cytochrome P450 from control rats using HPLC. Three new cytochrome P450s were detected in the starved rats. These cytochrome P450s were purified to homogeneity. One of them was P450 DM, judging from spectral properties, catalytic activity, and the NH2-terminal sequence. The two other forms were designated P450 3b and 4b. The minimum molecular weights of P450 3b and 4b were 53,000 and 52,000, respectively, and their CO-reduced absorption maxima were at 449 and 452 nm, respectively. P450 3b metabolized aminopyrine, N-nitrosodimethylamine, 7-ethoxycoumarin, and lauric acid, but with low activity. P450 4b was efficient in lauric acid ω- and (ω-1)-hydroxylation only. The spectral properties, catalytic activity, peptide map, and NH2-terminal sequence of P450 4b agreed with those of P450 K-5. P450 3b was a new cytochrome P450, judged by these criteria.

References (55)

  • S. Fujita et al.

    Biochem. Pharmacol

    (1985)
  • K.W. Miller et al.

    Arch. Biochem. Biophys

    (1984)
  • T. Nakajima et al.

    Toxicol. Appl. Pharmacol

    (1979)
  • N.A. Lorr et al.

    Toxicol. Appl. Pharmacol

    (1984)
  • J. Hong et al.

    Biochem. Biophys. Res. Commun

    (1987)
  • C.J. Patten et al.

    Arch. Biochem. Biophys

    (1986)
  • L.V. Favreau et al.

    J. Biol. Chem

    (1987)
  • S. Imaoka et al.

    Biochem. Biophys. Res. Commun

    (1988)
  • Y. Yamazoe et al.

    Arch. Biochem. Biophys

    (1989)
  • Y. Funae et al.

    Biochim. Biophys. Acta

    (1985)
  • Y. Funae et al.

    Biochim. Biophys. Acta

    (1987)
  • S. Imaoka et al.

    Arch. Biochem. Biophys

    (1988)
  • S. Imaoka et al.

    Biochim. Biophys. Acta

    (1987)
  • T. Omura et al.

    J. Biol. Chem

    (1964)
  • O.H. Lowry et al.

    J. Biol. Chem

    (1951)
  • S. Imaoka et al.

    Biochem. Biophys. Res. Commun

    (1986)
  • D.E. Ryan et al.

    J. Biol. Chem

    (1979)
  • D.E. Ryan et al.

    Arch. Biochem. Biophys

    (1982)
  • D.E. Ryan et al.

    J. Biol. Chem

    (1984)
  • D.E. Ryan et al.

    J. Biol. Chem

    (1985)
  • D.J. Waxman

    J. Biol. Chem

    (1984)
  • I. Jansson et al.

    J. Biol. Chem

    (1985)
  • J.E. Pettersen et al.

    Clin. Chim. Acta

    (1972)
  • J.E. Pettersen

    Clin. Chim. Acta

    (1972)
  • A.J. Sonderfan et al.

    Arch. Biochem. Biophys

    (1987)
  • K.E. Thummel et al.

    Arch. Biochem. Biophys

    (1988)
  • W. Levin et al.

    Arch. Biochem. Biophys

    (1987)
  • Cited by (0)

    View full text