title: Cholesterol metabolites exported from human brain.
abstract: The human brain contains approximately 25% of the body's cholesterol. The brain is separated from the circulation by the blood brain barrier. While cholesterol will not passes this barrier, oxygenated forms of cholesterol can cross the barrier. Here by measuring the difference in the oxysterol content of blood plasma in the jugular vein and in a forearm vein by mass spectrometry (MS) we were able to determine the flux of more than 20 cholesterol metabolites between brain and the circulation. We confirm that 24S-hydroxycholesterol is exported from brain at a rate of about 2-3mg/24h. Gas chromatography (GC)-MS data shows that the cholesterol metabolites 5α-hydroxy-6-oxocholesterol (3β,5α-dihydroxycholestan-6-one), 7β-hydroxycholesterol and 7-oxocholesterol, generally considered to be formed through reactive oxygen species, are similarly exported from brain at rates of about 0.1, 2 and 2mg/24h, respectively. Although not to statistical significance both GC-MS and liquid chromatography (LC)-MS methods indicate that (25R)26-hydroxycholesterol is imported to brain, while LC-MS indicates that 7α-hydroxy-3-oxocholest-4-enoic acid is exported from brain.
authors: Department of Medico-Surgical Sciences and Biotechnology, Sapienza University of Rome, corso della Repubblica 79, Latina 04100, Italy.
authors: Luigi
authors: L
authors: Iuliano
authors: College of Medicine, Grove Building, Swansea University, Singleton Park, Swansea SA2 8PP, UK.
authors: Peter J
authors: PJ
authors: Crick
authors: Department of Medico-Surgical Sciences and Biotechnology, Sapienza University of Rome, corso della Repubblica 79, Latina 04100, Italy.
authors: Chiara
authors: C
authors: Zerbinati
authors: Department of Anesthesiology and Intensive Care, Sapienza University of Rome, vial del Policlinico 163, Rome 00161, Italy.
authors: Luigi
authors: L
authors: Tritapepe
authors: College of Medicine, Grove Building, Swansea University, Singleton Park, Swansea SA2 8PP, UK.
authors: Jonas
authors: J
authors: Abdel-Khalik
authors: UMR 1037 INSERM-University Toulouse III, Cancer Research Center of Toulouse, and Institut Claudius Regaud, 31052 Toulouse, France.
authors: Marc
authors: M
authors: Poirot
authors: College of Medicine, Grove Building, Swansea University, Singleton Park, Swansea SA2 8PP, UK. Electronic address: y.wang@swansea.ac.uk.
authors: Yuqin
authors: Y
authors: Wang
authors: College of Medicine, Grove Building, Swansea University, Singleton Park, Swansea SA2 8PP, UK. Electronic address: w.j.griffiths@swansea.ac.uk.
authors: William J
authors: WJ
authors: Griffiths
mesh_terms: D001921:Brain / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D002853:Chromatography, Liquid; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D055442:Metabolome
chemical_list: D002784:Cholesterol
keywords: 24S-hydroxycholesterol; GC–MS; LC–MS; Oxysterol