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Biochem Biophys Res Commun. 2014 Jun 27;449(2):229-34. doi: 10.1016/j.bbrc.2014.05.012. Epub 2014 May 14.

24S,25-Epoxycholesterol in mouse and rat brain.

Author information

1
Clinical Laboratory, Jinan Infectious Disease Hospital, Shandong University, Jinan, Shandong, China. Electronic address: ycw7173@163.com.
2
UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.
3
Institute of Mass Spectrometry, College of Medicine, Grove Building, Swansea University, Singleton Park, Swansea SA2 8PP, UK.
4
Endocrinology Unit, BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
5
Institute of Mass Spectrometry, College of Medicine, Grove Building, Swansea University, Singleton Park, Swansea SA2 8PP, UK. Electronic address: w.j.griffiths@swansea.ac.uk.

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.

KEYWORDS:

24S,25-Epoxycholesterol; 24S-hydroxycholesterol; 25-epoxide; 3β,7α-Dihydroxycholest-5-en-24S; Brain; Cytochrome P450 7b1

PMID:
24832732
PMCID:
PMC4053837
DOI:
10.1016/j.bbrc.2014.05.012
[Indexed for MEDLINE]
Free PMC Article

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