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Analysis of bioactive oxysterols in newborn mouse brain by liquid chromatography - mass spectrometry / A Meljon; S Theofilopoulos; C. H. L Shackleton; G. L Watson; N. B Javitt; H.-J Knolker; R Saini; E Arenas; Y Wang; W. J Griffiths

The Journal of Lipid Research

Swansea University Author: Griffiths, William

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DOI (Published version): 10.1194/jlr.D028233

Abstract

Unesterified cholesterol is a major component of plasma membranes. In the brain of the adult it is mostly found in myelin sheaths where it plays a major architectural role. In the newborn mouse little myelination of neurons has occurred and much of this sterol comprises a metabolically active pool....

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Published in: The Journal of Lipid Research
ISSN: 0022-2275
Published: 2012
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URI: https://cronfa.swan.ac.uk/Record/cronfa12880
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Abstract: Unesterified cholesterol is a major component of plasma membranes. In the brain of the adult it is mostly found in myelin sheaths where it plays a major architectural role. In the newborn mouse little myelination of neurons has occurred and much of this sterol comprises a metabolically active pool. In the current study we have accessed this metabolically active pool and using liquid chromatography – mass spectrometry have identified cholesterol precursors and metabolites. While desmosterol and 24S-hydroxycholesterol represent the major precursor and metabolite respectively, other steroids including the oxysterols 22-oxocholesterol, 22R-hydroxycholesterol and 20R,22R-dihydroxycholesterol and the C21-neurosteroid progesterone were identified. 24S,25-Epoxycholesterol formed in parallel to cholesterol was also found to be a major sterol in newborn brain. Like 24S- and 22R-hydroxycholesterols, and also desmosterol, 24S,25-epoxycholesterol is a ligand to the liver X receptors which are expressed in brain. The desmosterol metabolites (24Z),26-, (24E),26- and 7α-hydroxydesmosterol were identified in brain for the first time.
Keywords: Sterol, Liver X Receptor, Desmosterol, Cholesterol, 24S-Hydroxycholesterol, 24S,25-Epoxycholesterol, derivatisation.
College: Swansea University Medical School