| Institution: | 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 |
| 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. |
