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Identification and characterization of a mouse oxysterol 7alpha-hydroxylase cDNA.

TitleIdentification and characterization of a mouse oxysterol 7alpha-hydroxylase cDNA.
Publication TypeJournal Article
Year of Publication1997
AuthorsSchwarz M, Lund EG, Lathe R, Björkhem I, Russell DW
JournalJ Biol Chem
Date Published1997 Sep 19
KeywordsAnimals, Cytochrome P-450 Enzyme System, DNA, Complementary, Gas Chromatography-Mass Spectrometry, Gene Expression Regulation, Enzymologic, Liver, Mice, RNA, Messenger, Species Specificity, Steroid Hydroxylases

The synthesis of essential 7alpha-hydroxylated bile acids in the liver is mediated by two pathways that involve distinct 7alpha-hydroxylases. One pathway is initiated in the endoplasmic reticulum by cholesterol 7alpha-hydroxylase, a well studied cytochrome P450 enzyme. A second pathway is initiated by a less well defined oxysterol 7alpha-hydroxylase. Here, we show that a mouse hepatic oxysterol 7alpha-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 7alpha-hydroxylase. Cyp7b1 mRNA and protein are induced in the third week of life commensurate with an increase in hepatic oxysterol 7alpha-hydroxylase activity. In the adult mouse, dietary cholesterol or colestipol induce cholesterol 7alpha-hydroxylase mRNA levels but do not affect oxysterol 7alpha-hydroxylase enzyme activity, mRNA, or protein levels. Cholesterol 7alpha-hydroxylase mRNA is reduced to undetectable levels in response to bile acids, whereas expression of oxysterol 7alpha-hydroxylase is modestly decreased. The liver thus maintains the capacity to synthesize 7alpha-hydroxylated bile acids regardless of dietary composition, underscoring the central role of 7alpha-hydroxylated bile acids in lipid metabolism.

Alternate JournalJ. Biol. Chem.
PubMed ID9295351
Grant ListHL20948 / HL / NHLBI NIH HHS / United States