Expression cloning of an oxysterol 7α-hydroxylase selective for 24- hydroxycholesterol

Jia Li-Hawkins, Erik G. Lund, Amy D. Bronson, David W. Russell

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

The synthesis of 7α-hydroxylated bile acids from oxysterols requires an oxysterol 7α-hydroxylase encoded by the Cyp7b1 locus. As expected, mice deficient in this enzyme have elevated plasma and tissue levels of 25- and 27-hydroxycholesterol; however, levels of another major oxysterol, 24- hydroxycholesterol, are not increased in these mice, suggesting the presence of another oxysterol 7α-hydroxylase. Here, we describe the cloning and characterization of murine and human cDNAs and genes that encode a second oxysterol 7α-hydroxylase. The genes contain 12 exons and are located on chromosome 6 in the human (CYP39A1 locus) and in a syntenic position on chromosome 17 in the mouse (Cyp39a1 locus). CYP39A1 is a microsomal cytochrome P450 enzyme that has preference for 24-hydroxycholesterol and is expressed in the liver. The levels of hepatic CYP39A1 mRNA do not change in response to dietary cholesterol, bile acids, or a bile acid-binding resin, unlike those encoding other sterol 7α-hydroxylases. Hepatic CYP39A1 expression is sexually dimorphic (female > male), which is opposite that of CYP7B1 (male > female). We conclude that oxysterol 7α-hydroxylases with different substrate specificities exist in mice and humans and that sexually dimorphic expression patterns of these enzymes in the mouse may underlie differences in bile acid metabolism between the sexes.

Original languageEnglish (US)
Pages (from-to)16543-16549
Number of pages7
JournalJournal of Biological Chemistry
Volume275
Issue number22
DOIs
StatePublished - Jun 2 2000

Fingerprint

Cloning
Mixed Function Oxygenases
Organism Cloning
Bile Acids and Salts
Chromosomes
Cytochrome P-450 Enzyme System
Genes
Liver
Dietary Cholesterol
Sterols
Enzymes
Chromosomes, Human, Pair 17
Chromosomes, Human, Pair 6
Metabolism
Substrate Specificity
Exons
Resins
Complementary DNA
24-hydroxycholesterol
Oxysterols

ASJC Scopus subject areas

  • Biochemistry

Cite this

Expression cloning of an oxysterol 7α-hydroxylase selective for 24- hydroxycholesterol. / Li-Hawkins, Jia; Lund, Erik G.; Bronson, Amy D.; Russell, David W.

In: Journal of Biological Chemistry, Vol. 275, No. 22, 02.06.2000, p. 16543-16549.

Research output: Contribution to journalArticle

Li-Hawkins, Jia ; Lund, Erik G. ; Bronson, Amy D. ; Russell, David W. / Expression cloning of an oxysterol 7α-hydroxylase selective for 24- hydroxycholesterol. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 22. pp. 16543-16549.
@article{084090404b72450eb118e6bdd298fe0b,
title = "Expression cloning of an oxysterol 7α-hydroxylase selective for 24- hydroxycholesterol",
abstract = "The synthesis of 7α-hydroxylated bile acids from oxysterols requires an oxysterol 7α-hydroxylase encoded by the Cyp7b1 locus. As expected, mice deficient in this enzyme have elevated plasma and tissue levels of 25- and 27-hydroxycholesterol; however, levels of another major oxysterol, 24- hydroxycholesterol, are not increased in these mice, suggesting the presence of another oxysterol 7α-hydroxylase. Here, we describe the cloning and characterization of murine and human cDNAs and genes that encode a second oxysterol 7α-hydroxylase. The genes contain 12 exons and are located on chromosome 6 in the human (CYP39A1 locus) and in a syntenic position on chromosome 17 in the mouse (Cyp39a1 locus). CYP39A1 is a microsomal cytochrome P450 enzyme that has preference for 24-hydroxycholesterol and is expressed in the liver. The levels of hepatic CYP39A1 mRNA do not change in response to dietary cholesterol, bile acids, or a bile acid-binding resin, unlike those encoding other sterol 7α-hydroxylases. Hepatic CYP39A1 expression is sexually dimorphic (female > male), which is opposite that of CYP7B1 (male > female). We conclude that oxysterol 7α-hydroxylases with different substrate specificities exist in mice and humans and that sexually dimorphic expression patterns of these enzymes in the mouse may underlie differences in bile acid metabolism between the sexes.",
author = "Jia Li-Hawkins and Lund, {Erik G.} and Bronson, {Amy D.} and Russell, {David W.}",
year = "2000",
month = "6",
day = "2",
doi = "10.1074/jbc.M001810200",
language = "English (US)",
volume = "275",
pages = "16543--16549",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "22",

}

TY - JOUR

T1 - Expression cloning of an oxysterol 7α-hydroxylase selective for 24- hydroxycholesterol

AU - Li-Hawkins, Jia

AU - Lund, Erik G.

AU - Bronson, Amy D.

AU - Russell, David W.

PY - 2000/6/2

Y1 - 2000/6/2

N2 - The synthesis of 7α-hydroxylated bile acids from oxysterols requires an oxysterol 7α-hydroxylase encoded by the Cyp7b1 locus. As expected, mice deficient in this enzyme have elevated plasma and tissue levels of 25- and 27-hydroxycholesterol; however, levels of another major oxysterol, 24- hydroxycholesterol, are not increased in these mice, suggesting the presence of another oxysterol 7α-hydroxylase. Here, we describe the cloning and characterization of murine and human cDNAs and genes that encode a second oxysterol 7α-hydroxylase. The genes contain 12 exons and are located on chromosome 6 in the human (CYP39A1 locus) and in a syntenic position on chromosome 17 in the mouse (Cyp39a1 locus). CYP39A1 is a microsomal cytochrome P450 enzyme that has preference for 24-hydroxycholesterol and is expressed in the liver. The levels of hepatic CYP39A1 mRNA do not change in response to dietary cholesterol, bile acids, or a bile acid-binding resin, unlike those encoding other sterol 7α-hydroxylases. Hepatic CYP39A1 expression is sexually dimorphic (female > male), which is opposite that of CYP7B1 (male > female). We conclude that oxysterol 7α-hydroxylases with different substrate specificities exist in mice and humans and that sexually dimorphic expression patterns of these enzymes in the mouse may underlie differences in bile acid metabolism between the sexes.

AB - The synthesis of 7α-hydroxylated bile acids from oxysterols requires an oxysterol 7α-hydroxylase encoded by the Cyp7b1 locus. As expected, mice deficient in this enzyme have elevated plasma and tissue levels of 25- and 27-hydroxycholesterol; however, levels of another major oxysterol, 24- hydroxycholesterol, are not increased in these mice, suggesting the presence of another oxysterol 7α-hydroxylase. Here, we describe the cloning and characterization of murine and human cDNAs and genes that encode a second oxysterol 7α-hydroxylase. The genes contain 12 exons and are located on chromosome 6 in the human (CYP39A1 locus) and in a syntenic position on chromosome 17 in the mouse (Cyp39a1 locus). CYP39A1 is a microsomal cytochrome P450 enzyme that has preference for 24-hydroxycholesterol and is expressed in the liver. The levels of hepatic CYP39A1 mRNA do not change in response to dietary cholesterol, bile acids, or a bile acid-binding resin, unlike those encoding other sterol 7α-hydroxylases. Hepatic CYP39A1 expression is sexually dimorphic (female > male), which is opposite that of CYP7B1 (male > female). We conclude that oxysterol 7α-hydroxylases with different substrate specificities exist in mice and humans and that sexually dimorphic expression patterns of these enzymes in the mouse may underlie differences in bile acid metabolism between the sexes.

UR - http://www.scopus.com/inward/record.url?scp=0034595650&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034595650&partnerID=8YFLogxK

U2 - 10.1074/jbc.M001810200

DO - 10.1074/jbc.M001810200

M3 - Article

C2 - 10748047

AN - SCOPUS:0034595650

VL - 275

SP - 16543

EP - 16549

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 22

ER -