24S,25-Epoxycholesterol in mouse and rat brain |
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| Authors: | Yuchen Wang Kersti Karu Anna Meljon John Turton Joyce L. Yau Jonathan R. Seckl Yuqin Wang William J. Griffiths |
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| Affiliation: | 1. Clinical Laboratory, Jinan Infectious Disease Hospital, Shandong University, Jinan, Shandong, China;2. UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK;3. Institute of Mass Spectrometry, College of Medicine, Grove Building, Swansea University, Singleton Park, Swansea SA2 8PP, UK;4. Endocrinology Unit, BHF Centre for Cardiovascular Science, The Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK |
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| Abstract: | 24S,25-Epoxycholesterol is formed in a shunt of the mevalonate pathway that produces cholesterol. It is one of the most potent known activators of the liver X receptors and can inhibit sterol regulatory element-binding protein processing. Until recently analysis of 24S,25-epoxycholesterol at high sensitivity has been precluded by its thermal lability and lack of a strong chromophore. Here we report on the analysis of 24S,25-epoxycholesterol in rodent brain where its level was determined to be of the order of 0.4–1.4 μg/g wet weight in both adult mouse and rat. For comparison the level of 24S-hydroxycholesterol in brain of both rodents was of the order of 20 μg/g, while that of cholesterol in mouse was 10–20 mg/g. By exploiting knockout mice for the enzyme oxysterol 7α-hydroxylase (Cyp7b1) we show that this enzymes is important for the subsequent metabolism of the 24S,25-epoxide. |
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| Keywords: | HMG-CoA, 3-hydroxy-3-methyl-glutaryl-CoA APCI, atmospheric pressure chemical ionisation API, atmospheric pressure ionisation BBB, blood brain barrier CNS, central nervous system Ctx, cortex CYP or Cyp, cytochrome P450 DDA, data dependent analysis ER, endoplasmic reticulum ESI, electrospray ionisation GC, gas chromatography GP, Girard P Insig, insulin-induced gene LIT, linear ion-trap LC, liquid chromatography LXRs or Lxrs, liver X receptors MS, mass spectrometry or mass spectrum MSn, mass spectrometry with multistage fragmentation MRM, multiple reaction monitoring RICs, reconstructed ion chromatogram SCAP, SREBP-cleavage activating protein SREBP-2, sterol regulatory element-binding protein-2 Vm, ventral midbrain wt, wild type |
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