TY - JOUR
T1 - Identification and characterization of a mouse oxysterol 7α-hydroxylase cDNA
AU - Schwarz, Margrit
AU - Lund, Erik G.
AU - Lathe, Richard
AU - Björkhem, Ingemar
AU - Russell, David W.
PY - 1997/9/19
Y1 - 1997/9/19
N2 - The synthesis of essential 7α-hydroxylated bile acids in the liver is mediated by two pathways that involve distinct 7α-hydroxylases. One pathway is initiated in the endoplasmic reticulum by cholesterol 7α-hydroxylase, a well studied cytochrome P450 enzyme. A second pathway is initiated by a less well defined oxysterol 7α-hydroxylase. Here, we show that a mouse hepatic oxysterol 7α-hydroxylase is encoded by Cyp7b1, a cytochrome P450 cDNA originally isolated from the hippocampus. Expression of a Cyp7b1 cDNA in cultured cells produces an enzyme with the same biochemical and pharmacological properties as those of the hepatic oxysterol 7α-hydroxylase. Cyp7b1 mRNA and protein are induced in the third week of life commensurate with an increase in hepatic oxysterol 7α-hydroxylase activity. In the adult mouse, dietary cholesterol or colestipol induce cholesterol 7α-hydroxylase mRNA levels but do not affect oxysterol 7α-hydroxylase enzyme activity, mRNA, or protein levels. Cholesterol 7α-hydroxylase mRNA is reduced to undetectable levels in response to bile acids, whereas expression of oxysterol 7α-hydroxylase is modestly decreased. The liver thus maintains the capacity to synthesize 7α-hydroxylated bile acids regardless of dietary composition, underscoring the central role of 7α-hydroxylated bile acids in lipid metabolism.
AB - The synthesis of essential 7α-hydroxylated bile acids in the liver is mediated by two pathways that involve distinct 7α-hydroxylases. One pathway is initiated in the endoplasmic reticulum by cholesterol 7α-hydroxylase, a well studied cytochrome P450 enzyme. A second pathway is initiated by a less well defined oxysterol 7α-hydroxylase. Here, we show that a mouse hepatic oxysterol 7α-hydroxylase is encoded by Cyp7b1, a cytochrome P450 cDNA originally isolated from the hippocampus. Expression of a Cyp7b1 cDNA in cultured cells produces an enzyme with the same biochemical and pharmacological properties as those of the hepatic oxysterol 7α-hydroxylase. Cyp7b1 mRNA and protein are induced in the third week of life commensurate with an increase in hepatic oxysterol 7α-hydroxylase activity. In the adult mouse, dietary cholesterol or colestipol induce cholesterol 7α-hydroxylase mRNA levels but do not affect oxysterol 7α-hydroxylase enzyme activity, mRNA, or protein levels. Cholesterol 7α-hydroxylase mRNA is reduced to undetectable levels in response to bile acids, whereas expression of oxysterol 7α-hydroxylase is modestly decreased. The liver thus maintains the capacity to synthesize 7α-hydroxylated bile acids regardless of dietary composition, underscoring the central role of 7α-hydroxylated bile acids in lipid metabolism.
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U2 - 10.1074/jbc.272.38.23995
DO - 10.1074/jbc.272.38.23995
M3 - Article
C2 - 9295351
AN - SCOPUS:0030845921
SN - 0021-9258
VL - 272
SP - 23995
EP - 24001
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 38
ER -