Heterogeneity of rat liver parenchyma in cholesterol 7 alpha-hydroxylase and bile acid synthesis

B Ugele, H J Kempen, J M Kempen, R Gebhardt, P Meijer, H J Burger, H M Princen, B Ugele, H J Kempen, J M Kempen, R Gebhardt, P Meijer, H J Burger, H M Princen

Abstract

Periportal and perivenous hepatocytes were isolated from rat liver by digitonin/collagenase perfusion for investigating the acinar distribution of bile acid synthesis. The specific activity of cholesterol 7 alpha-hydroxylase (EC 1.14.13.17) was 7.9-fold higher in perivenous cells than in periportal hepatocytes. Mass production of bile acids differed 4.4-fold between cultured perivenous and periportal hepatocytes. In contrast, the levels of free cholesterol in homogenates and microsomes derived from both subfractions were similar. Feeding of rats with the bile-acid-sequestering anion-exchange resin colestid resulted in a pronounced stimulation of cholesterol 7 alpha-hydroxylase activity and bile acid mass production, but decreased the perivenous/periportal ratio of both parameters. These results demonstrate that bile acid mass production, but decreased the perivenous hepatocytes, possibly owing to feedback suppression by bile acids from the enterohepatic circulation. Furthermore, the opposite acinar localization of cholesterol and bile acid biosynthesis provides an interesting alternative to current views of the regulation of their metabolic pathways.

References

    1. Hepatology. 1989 Jan;9(1):22-8
    1. J Biol Chem. 1951 Nov;193(1):265-75
    1. J Clin Invest. 1989 Jul;84(1):173-80
    1. Physiol Rev. 1989 Jul;69(3):708-64
    1. Arch Biochem Biophys. 1965 Aug;111(2):448-60
    1. J Lipid Res. 1969 Nov;10(6):646-55
    1. J Biol Chem. 1974 Oct 10;249(19):6052-6
    1. Annu Rev Biochem. 1975;44:233-53
    1. Methods Cell Biol. 1976;13:29-83
    1. J Lipid Res. 1977 Mar;18(2):135-53
    1. Eur J Biochem. 1978 Jan 16;82(2):419-29
    1. J Lipid Res. 1978 Sep;19(7):872-8
    1. J Lipid Res. 1978 Nov;19(8):1068-70
    1. Histochemistry. 1979 Feb 26;60(1):43-52
    1. Am J Physiol. 1980 Mar;238(3):G233-7
    1. Adv Anat Embryol Cell Biol. 1980;60:1-54
    1. Mol Pharmacol. 1980 Sep;18(2):304-12
    1. Mol Pharmacol. 1981 May;19(3):513-6
    1. Biochim Biophys Acta. 1981 Jul 24;665(1):81-7
    1. Steroids. 1981 Nov;38(5):495-509
    1. J Lipid Res. 1982 Aug;23(6):823-30
    1. Am J Physiol. 1982 Dec;243(6):G455-62
    1. J Biol Chem. 1983 Mar 25;258(6):3661-7
    1. J Biol Chem. 1983 Apr 10;258(7):4079-82
    1. J Cell Sci. 1982 Aug;56:233-44
    1. J Lipid Res. 1983 Mar;24(3):316-23
    1. EMBO J. 1983;2(4):567-70
    1. Proc Natl Acad Sci U S A. 1984 Sep;81(17):5556-60
    1. Biochem J. 1985 Jun 15;228(3):757-60
    1. Biochem J. 1985 Jul 1;229(1):221-6
    1. J Biol Chem. 1985 Nov 5;260(25):13459-63
    1. Enzyme. 1986;35(3):161-80
    1. J Clin Invest. 1986 Oct;78(4):1064-71
    1. J Pharmacol Exp Ther. 1987 Feb;240(2):663-7
    1. Mol Pharmacol. 1987 Aug;32(1):189-94
    1. FASEB J. 1988 Feb;2(2):152-6
    1. J Lipid Res. 1988 Feb;29(2):136-43
    1. Hepatology. 1988 Jul-Aug;8(4):822-30
    1. Anal Biochem. 1988 May 15;171(1):158-65
    1. Biochem Biophys Res Commun. 1988 Sep 15;155(2):850-6
    1. J Lipid Res. 1988 Jun;29(6):781-96
    1. Hepatology. 1989 Jan;9(1):154-60
    1. Biochem Biophys Res Commun. 1989 Jul 31;162(2):619-25
    1. Cell Biol Toxicol. 1986 Mar;2(1):9-20
    1. Biochem J. 1989 Aug 15;262(1):341-8
    1. Biochim Biophys Acta. 1990 Feb 23;1042(3):386-94
    1. Am J Physiol. 1990 Apr;258(4 Pt 1):C700-12
    1. Hepatology. 1990 Nov;12(5):1209-15
    1. Biochim Biophys Acta. 1989 Feb 6;1001(2):176-84

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する