24S,25-Epoxycholesterol in mouse and rat brain

[Display omitted] •24S,25-Epoxycholesterol identified and quantified in rodent brain.•Knock out of Cyp27a1 leads to a decrease in 24S,25-epoxycholesterol.•Knock out of Cyp7b1 leads to an increase in 24S,25-epoxycholesterol.•24S,25-Epoxycholesterol is metabolised by Cyp7b1 but not Cyp27a1. 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 0.4–1.4μg/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 20μg/g, while that of cholesterol in mouse was 10–20mg/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.