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Biochem Biophys Res Commun. 2014 Apr 11;446(3):768-74. doi: 10.1016/j.bbrc.2014.01.153. Epub 2014 Jan 31.

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

Author information

1
Institute of Mass Spectrometry, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK.
2
Institute of Mass Spectrometry, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK. Electronic address: w.j.griffiths@swansea.ac.uk.

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.

KEYWORDS:

24R-Hydroxycholesterol; 24S,25-Epoxycholesterol; 24S-Hydroxycholesterol; Brain; Cyp46a1; Oxysterol

PMID:
24491562
PMCID:
PMC4000437
DOI:
10.1016/j.bbrc.2014.01.153
[Indexed for MEDLINE]
Free PMC Article

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