Insensitivity of ubiquinone biosynthesis in glioblastoma cells to an epileptogenic drug, U18666A.
To investigate the perturbation of ubiquinone biosynthesis by a hypocholesterolemic drug, 3 beta-(2-diethylaminoethoxy)androst-5-en-17-one hydrochloride (U18666A), we measured the incorporation of radioactive mevalonate, methionine, tyrosine, and 4-hydroxybenzoic acid into ubiquinone in glioblastoma cells. These four precursors unanimously showed that ubiquinone biosynthesis was not significantly altered by U18666A, which blocked cholesterol biosynthesis at steps beyond mevalonate formation. The fluctuation of the endogenous mevalonate level had little effect on ubiquinone biosynthesis, implying the relative stability of cellular ubiquinone biosynthesis. Furthermore, exogenously added mevalonate did not have an appreciable effect on ubiquinone biosynthesis. The major ubiquinone produced in rat glioblastoma cells was identified as ubiquinone-9. The mevalonate-derived products accumulated in the U18666A-treated cells differed significantly from those reported in a broken cell study, suggesting the existence of delicate mechanisms regulating the formation of cholesterol intermediates.
D000736:Androstenes / Q000494:pharmacology*; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D002460:Cell Line; D005910:Glioma / Q000378:metabolism*; D062385:Hydroxybenzoates / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin; D008715:Methionine / Q000378:metabolism; D008798:Mevalonic Acid / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology; D010226:Parabens; D051381:Rats; D014443:Tyrosine / Q000378:metabolism; D014451:Ubiquinone / Q000096:biosynthesis*
D000736:Androstenes; D000924:Anticholesteremic Agents; D062385:Hydroxybenzoates; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009281:Naphthalenes; D010226:Parabens; D014451:Ubiquinone; C006261:3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one; D014443:Tyrosine; D008148:Lovastatin; D008715:Methionine; C038193:4-hydroxybenzoic acid; C030571:ubiquinone 9; D008798:Mevalonic Acid