Analysis of bioactive oxysterols in newborn mouse brain by LC/MS

Journal of Lipid Research

Hans-Joachim Knölker¹  Gordon L. Watson²  Cedric H.L. Shackleton²  Ratni Saini³  Ernest Arenas³  Norman B. Javitt⁴  Anna Meljon⁵  Spyridon Theofilopoulos⁶  Yuqin Wang⁶  William J. Griffiths⁷ 

[1] and;Children's Hospital Oakland Research Institute, Oakland, CA;Department Chemie, Technische Universität Dresden, Dresden, Germany;Department of Medicine, NYU School of Medicine, New York, NY;Institute of Mass Spectrometry, College of Medicine, Swansea, UK;Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden;To whom correspondence should be addressed.;

关键词: sterol;    liver X receptor;    desmosterol;    cholesterol;    24S-hydroxycholesterol;    24S,25-epoxycholesterol;   

DOI  :  

来源: DOAJ

【 摘 要 】

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

【 授权许可】

Unknown