7α-hyroxylation of 127-hydroxycholesterol: Biologic role in the regulation of cholesterol synthesis

Kumiko O. Martin, Allison B. Reiss, Richard Lathe, Norman B. Javitt*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The report of a novel cytochrome P450 enzyme in mouse hippocampus (cyp7b) with close homology to cholesterol 7α-hydroxylase led us to determine the substrate specificity with respect to 27-hydroxycholesterol, known to be a potent inhibitor of cholesterol synthesis. Transfection of 293/T cells with pcDNA3.1(+)-mycp7b as followed by metabolism of 2.5 μM 27- hydroxycholesterol to the 7α-hydroxy intermediate, cholest-5- ene,3β,7α,27-triol, with complete loss of down-regulation of cholesterol synthesis. Addition of 5 μM and 10 μM concentrations of the triol to HepG2 and CHO cells, respectively, also did not reduce cholesterol synthesis. The contrast between the biologic effect on cholesterol synthesis by these two C27 hydroxysterols and the wide tissue distribution of both cholesterol 27- hydroxylase and hydroxysterol 7α-hydroxylase implies local regulatory effects prior to their further catabolism in the liver to chenodeoxycholic and cholic acids.

Original languageEnglish
Pages (from-to)1053-1058
Number of pages6
JournalJournal of lipid research
Volume38
Issue number5
Publication statusPublished - May 1997

Keywords

  • 27-hydroxycholesterol 7α-hydroxylase
  • 293/T cells
  • CDNA-mcyp7b
  • CHO cells
  • Cholest-5-ene-3β,7α,27- triol
  • Cholesterol 7α- hydroxylase
  • Transfection

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