24S,25-Epoxycholesterol in mouse and rat brain

Yuchen Wang, Kersti Karu, Anna Meljon, John Turton, Joyce L Yau, Jonathan R Seckl, Yuqin Wang, William J Griffiths

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

24S,25-Epoxycholesterol is formed in a shunt of the mevalonate pathway that produces cholesterol. It is one of the most potent known activators of the liver X receptors and can inhibit sterol regulatory element-binding protein processing. Until recently analysis of 24S,25-epoxycholesterol at high sensitivity has been precluded by its thermal lability and lack of a strong chromophore. Here we report on the analysis of 24S,25-epoxycholesterol in rodent brain where its level was determined to be of the order of 0.4-1.4μg/g wet weight in both adult mouse and rat. For comparison the level of 24S-hydroxycholesterol in brain of both rodents was of the order of 20μg/g, while that of cholesterol in mouse was 10-20mg/g. By exploiting knockout mice for the enzyme oxysterol 7α-hydroxylase (Cyp7b1) we show that this enzymes is important for the subsequent metabolism of the 24S,25-epoxide.

Original languageEnglish
Pages (from-to)229-34
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume449
Issue number2
DOIs
Publication statusPublished - 27 Jun 2014
Externally publishedYes

Bibliographical note

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

Keywords

  • Animals
  • Brain/metabolism
  • Cholesterol/analogs & derivatives
  • Cytochrome P450 Family 7
  • Female
  • Male
  • Metabolic Networks and Pathways
  • Mevalonic Acid/metabolism
  • Mice
  • Mice, Congenic
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Biological
  • Rats
  • Rats, Sprague-Dawley
  • Spectrometry, Mass, Electrospray Ionization
  • Steroid Hydroxylases/deficiency
  • Sterols/metabolism

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