Oxysterols in the brain of the cholesterol 24-hydroxylase knockout mouse.
Oxysterols are oxidised forms of cholesterol or its precursors. In this study we utilised the cholesterol 24-hydroxylase knockout mouse (Cyp46a1-/-) to study the sterol and oxysterol content of brain. Despite a great reduction in the abundance of 24S-hydroxycholesterol, the dominant metabolite of cholesterol in wild type brain, no other cholesterol metabolite was found to quantitatively replace this oxysterol in the Cyp46a1-/- mouse. Only minor amounts of other side-chain oxysterols including 22R-, 24R-, 25- and (25R),26-hydroxycholesterols were detected. In line with earlier studies, levels of cholesterol were similar in Cyp46a1-/- and wild type animals. However, the level of the cholesterol precursor, desomsterol, and its parallel metabolite formed via a shut of the mevalonate pathway, 24S,25-epoxycholesterol, were reduced in the Cyp46a1-/- mouse. The reduction in abundance of 24S,25-epoxycholesterol is interesting in light of a recent report indicating that this oxysterol promotes dopaminergic neurogenesis.
Institute of Mass Spectrometry, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK.
Anna
A
Meljon
Institute of Mass Spectrometry, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK.
Yuqin
Y
Wang
Institute of Mass Spectrometry, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK. Electronic address: w.j.griffiths@swansea.ac.uk.
William J
WJ
Griffiths
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002784:Cholesterol / Q000031:analogs & derivatives / Q000378:metabolism; D000072556:Cholesterol 24-Hydroxylase; D005260:Female; D006888:Hydroxycholesterols / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D013250:Steroid Hydroxylases / Q000235:genetics* / Q000378:metabolism
D006888:Hydroxycholesterols; C007042:cholest-5-ene-3 beta,26-diol; C044563:24-hydroxycholesterol; C028358:24,25-epoxycholesterol; D002784:Cholesterol; D013250:Steroid Hydroxylases; D000072556:Cholesterol 24-Hydroxylase
24R-Hydroxycholesterol; 24S,25-Epoxycholesterol; 24S-Hydroxycholesterol; Brain; Cyp46a1; Oxysterol