Figure 6

Endogenous 24( S ),25-epoxycholesterol regulates SREBP- and LXR-mediated transcription. (A) Under normal conditions, cholesterol synthesis is favoured but some 24,25EC is still produced. (B) Since oxidosqualene cyclase (OSC) preferentially cyclises 2,3(S):22(S),23-dioxidosqualene (DOS) over 2,3(S)-monooxidosqualene (MOS), partial inhibition of OSC favours synthesis of 24,25EC. (C) CHO-7 cells were incubated with increasing concentrations of GW534511X in the presence of [1-¹⁴C]-acetate for 24 h. Neutral lipid extracts were separated by thin-layer chromatography and bands corresponding to authentic cholesterol and 24,25EC were visualized by phosphorimager. This phosphorimage is representative of 3 separate experiments. (D-F) CHO-7 cells were transiently transfected for 24 h with phRL-TK Renilla internal control plasmid together with either (D) SRE-luc, (E) pGL3-hABCA1 wild-type or DR4 mutant, (F) LXRE-luc. Following transfection, cells were incubated for 24 h in the absence or presence of indicated concentrations of GW534511X. Data are presented as percentage change relative to (E) the pGL3-hABCA1 wild-type construct vehicle-treated control condition or (D, F) vehicle-treated control condition. (D, E, F) are means+SEM(n = 3 separate experiments); for (E) DR4 mutant are means+halfrange (n = 2 separate experiments).