Analysis of bioactive oxysterols in newborn mouse brain by LC/MS |
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| Authors: | Anna Meljon Spyridon Theofilopoulos Cedric H. L. Shackleton Gordon L. Watson Norman B. Javitt Hans-Joachim Kn?lker Ratni Saini Ernest Arenas Yuqin Wang William J. Griffiths |
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| Affiliation: | *Institute of Mass Spectrometry, College of Medicine, Swansea, UK;†Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden;§Children''s Hospital Oakland Research Institute, Oakland, CA;**Department of Medicine, NYU School of Medicine, New York, NY; and;††Department Chemie, Technische Universität Dresden, Dresden, Germany |
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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 LC/MS, have identified cholesterol precursors and metabolites. Although desmosterol and 24S-hydroxycholesterol represent the major precursor and metabolite, respectively, other steroids, including the oxysterols 22-oxocholesterol, 22R-hydroxycholesterol, 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 |
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| Keywords: | sterol liver X receptor desmosterol cholesterol 24S-hydroxycholesterol 24S 25-epoxycholesterol derivatization |
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