Synergistic action of two oxysterols in the lowering of HMG-CoA reductase activity in CHO-K1 cells.
3 beta-Hydroxy-5 alpha-cholest-8(14)-en-15-one (I) and (25R)-26-hydroxycholesterol (II), both potent regulators of sterol biosynthesis, have been found to show synergism in the reduction of the levels of HMG-CoA reductase activity in CHO-K1 cells. When equimolar concentrations of I and II were added in combination, synergistic reduction (p less than 0.0001) of enzyme activity was observed at total oxysterol concentrations of 0.1 microM, 0.2 microM, and 0.5 microM. Maximal synergistic effect in the lowering of reductase activity (28% greater than predicted) was observed at 0.1 microM total oxysterol concentration. Five additional experiments conducted with 50 nM oxysterols confirmed the synergistic effect at 0.1 microM total sterol concentration. These results suggest that the in vivo importance of I and II may be greater than that anticipated on the basis of the concentrations of the individual sterols.
Pinkerton
F D
FD
Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77251.
Pelley
R P
RP
Schroepfer
G J
GJ
D000704:Analysis of Variance; D000818:Animals; D016466:CHO Cells; D002783:Cholestenones / Q000494:pharmacology*; D002999:Clone Cells; D006224:Cricetinae; D004357:Drug Synergism; D006888:Hydroxycholesterols / Q000494:pharmacology*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007700:Kinetics
D002783:Cholestenones; D006888:Hydroxycholesterols; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C007042:cholest-5-ene-3 beta,26-diol; C015073:cholest-8(14)-en-3-ol-15-one; D006903:Hydroxymethylglutaryl CoA Reductases