24S,25-Epoxycholesterol in mouse and rat brain.
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.
Clinical Laboratory, Jinan Infectious Disease Hospital, Shandong University, Jinan, Shandong, China. Electronic address: ycw7173@163.com.
Yuchen
Y
Wang
UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.
Kersti
K
Karu
Institute of Mass Spectrometry, College of Medicine, Grove Building, Swansea University, Singleton Park, Swansea SA2 8PP, UK.
Anna
A
Meljon
UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.
John
J
Turton
Endocrinology Unit, BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
Joyce L
JL
Yau
Endocrinology Unit, BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
Jonathan R
JR
Seckl
Institute of Mass Spectrometry, College of Medicine, Grove Building, Swansea University, Singleton Park, Swansea SA2 8PP, UK.
Yuqin
Y
Wang
Institute of Mass Spectrometry, College of Medicine, Grove Building, 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; D000072474:Cytochrome P450 Family 7; D005260:Female; D008297:Male; D053858:Metabolic Networks and Pathways; D008798:Mevalonic Acid / Q000378:metabolism; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization; D013250:Steroid Hydroxylases / Q000172:deficiency / Q000235:genetics; D013261:Sterols / Q000378:metabolism
D013261:Sterols; C028358:24,25-epoxycholesterol; D002784:Cholesterol; D013250:Steroid Hydroxylases; D000072474:Cytochrome P450 Family 7; C097207:Cyp7b1 protein, mouse; D008798:Mevalonic Acid
24S,25-Epoxycholesterol; 24S-hydroxycholesterol; 25-epoxide; 3β,7α-Dihydroxycholest-5-en-24S; Brain; Cytochrome P450 7b1