Control of low density lipoprotein receptor gene promoter activity. Ketoconazole inhibits serum lipoprotein but not oxysterol suppression of gene transcription.
作者： K Takagi , J G Alvarez , M F Favata , J M Trzaskos , J F Strauss
DOI: 10.1016/S0021-9258(18)63865-7
关键词:
摘要: Abstract We have examined the effects of ketoconazole, a drug which inhibits enzymes involved in cholesterol biosynthesis and metabolism, on suppressive serum lipoproteins 25-hydroxycholesterol low density lipoprotein (LDL) receptor gene promoter activity. A LDL promoter-chloramphenicol acetyltransferase (CAT) fusion construct (pLDLR-CAT 6500) was transfected into JEG-3 choriocarcinoma cells, cells were cultured absence or presence serum, LDL, 25-hydroxycholesterol. Serum, + reduced chloramphenicol activity with pLDLR-CAT 6500, whereas these treatments had no effect upon enzyme control (pSV2CAT). Ketoconazole (50 microM) overcame suppression 6500 expression, but could not override combination significant expression pSV2CAT. The inhibited side chain cleavage appeared to impact ability take up LDL-carried lipids. Our observations are consistent idea that is metabolized an effector substance acts suppress transcription. generation this seems be sensitive ketoconazole.
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