Oxysterols in newborn mouse brain

Anna Meljon, Yuqin Wang, William J Griffiths

Research output: Contribution to conferencePoster

Abstract

Oxysterols are produced from cholesterol in enzymatic conversions catalysed by CYP enzymes or by
cholesterol 25-hydroxylase. Alternatively, they can be formed by interaction with endogenous ROS or by
autoxidation during sample preparation. In the past oxysterols were regarded as intermediates in steroid
hormone and bile acid biosynthesis, or as transport forms of cholesterol. Newer findings point to a role for
oxysterols as ligands to nuclear receptors e.g. LXR, FXR, PXR, and also to INSIG. More recently, oxysterols
were shown to modulate immune response and neurogenesis.
In the present study we profiled the sterol and oxysterol content of newborn mouse brain. Prior to MS analysis,
the sterol/oxysterol content of brain was treated with cholesterol oxidase and derivatised with Girard P hydrazine
then separated by LC. By inclusion of an isotope-labelled standard this allowed the quantification of
sterols/oxysterols with 3β-hydroxy-5-ene or 3β-hydroxy-5α-hydrogen structure. With this protocol we quantified
a wide range of oxysterols including 22R-hydroxycholesterol, 24S-hydroxycholesterol, 7α-hydroxycholesterol,
7β-hydroxycholesterol, 6α-hydroxycholesterol, 24S,25-epoxycholesterol, 22-oxocholesterol, and 24-
oxocholesterol. The most abundant oxysterols were 24S-hydroxycholesterol and 24S,25-epoxycholesterol.
24S-Hydroxylation is the major pathway of cholesterol exertion from CNS and reflects cholesterol metabolism in
brain tissue.
High levels of 24S,25-epoxycholesterol in foetal brain were reported previously. Unlike other oxysterols, 24S,25-
epoxycholesterol is formed via a shunt of the mevalonate pathway, not by enzymatic hydroxylation of
cholesterol. 24S,25-Epoxycholesterol can affect cholesterol homeostasis in different ways: as an agonist to the
LXRs and also by suppressing the processing of SREBP-2 to its active form as a transcription factor. The
presence of 22-oxocholesterol is a surprising result. Brain localization of this steroid has not been previously
reported in the literature and needs a further investigation.
Original languageEnglish
Publication statusPublished - 02 May 2011
EventLIPID MAPS Annual Meeting: LIPID MAPS Annual Meeting 2011: Lipidomics Impact on Cell Biology, Cancer, and Metabolic Diseases - Scripps Seaside Forum, La Jolla, United States
Duration: 02 May 201102 May 2011
https://www.lipidmaps.org/meetings/2011annual/index.html

Conference

ConferenceLIPID MAPS Annual Meeting
CountryUnited States
CityLa Jolla
Period02/05/201102/05/2011
Internet address

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  • Cite this

    Meljon, A., Wang, Y., & Griffiths, W. J. (2011). Oxysterols in newborn mouse brain. Poster session presented at LIPID MAPS Annual Meeting, La Jolla, United States.