Oxysterols in the brain of the cholesterol 24-hydroxylase knockout mouse

Anna Meljon, Yuqin Wang, William J Griffiths

Research output: Contribution to journalArticle

28 Citations (Scopus)
138 Downloads (Pure)

Abstract

Oxysterols are oxidised forms of cholesterol or its precursors. In this study we utilised the cholesterol 24-hydroxylase knockout mouse (Cyp46a1-/-) to study the sterol and oxysterol content of brain. Despite a great reduction in the abundance of 24S-hydroxycholesterol, the dominant metabolite of cholesterol in wild type brain, no other cholesterol metabolite was found to quantitatively replace this oxysterol in the Cyp46a1-/- mouse. Only minor amounts of other side-chain oxysterols including 22R-, 24R-, 25- and (25R),26-hydroxycholesterols were detected. In line with earlier studies, levels of cholesterol were similar in Cyp46a1-/- and wild type animals. However, the level of the cholesterol precursor, desomsterol, and its parallel metabolite formed via a shut of the mevalonate pathway, 24S,25-epoxycholesterol, were reduced in the Cyp46a1-/- mouse. The reduction in abundance of 24S,25-epoxycholesterol is interesting in light of a recent report indicating that this oxysterol promotes dopaminergic neurogenesis.

Original languageEnglish
Pages (from-to)768-774
JournalBiochemical and Biophysical Research Communications
Volume446
Issue number3
Early online date31 Jan 2014
DOIs
Publication statusPublished - 11 Apr 2014

Bibliographical note

Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Keywords

  • Animals
  • Brain/metabolism
  • Cholesterol/analogs & derivatives
  • Cholesterol 24-Hydroxylase
  • Female
  • Hydroxycholesterols/metabolism
  • Mice
  • Mice, Knockout
  • Steroid Hydroxylases/genetics

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