-transparent.png){kind=logo}
Ketoconazole, an imidazole derivative, is a member of a class of metabolic inhibitors acting specifically at cytochrome-P450 mediated reactions. We studied the effects of this compound on cholesterol synthesis, and on HMG-CoA reductase and LDL receptor activities, in cultures of human hepatoma cell line Hep G2. Ketoconazole, added in concentrations of 2-100 microM, inhibited cholesterol synthesis, and caused accumulation of lanosterol and dihydrolanosterol. Total mass formation of sterols was depressed. After 20 hr preincubation of the cells with the drug in these concentrations, activity of HMG-CoA reductase was markedly decreased, while the receptor-mediated binding, uptake and degradation of human LDL were increased. This increase is at least partly due to a higher affinity of LDL for its receptor. Ketoconazole prevented the fall in LDL-receptor activity caused by preincubation with LDL, whereas it did not affect the suppression caused by preincubation with exogenous mevalonate. These findings are discussed with respect to the involvement of endogenous sterol and non-sterol effectors of reductase and receptor activities.
H J Kempen, and
K van Son, and
L H Cohen, and
M Griffioen, and
H Verboom, and
L Havekes
June 1999,
Biochemical and biophysical research communications,
H J Kempen, and
K van Son, and
L H Cohen, and
M Griffioen, and
H Verboom, and
L Havekes
October 1992,
Journal of cell science,
H J Kempen, and
K van Son, and
L H Cohen, and
M Griffioen, and
H Verboom, and
L Havekes
August 2000,
The Journal of pharmacology and experimental therapeutics,
H J Kempen, and
K van Son, and
L H Cohen, and
M Griffioen, and
H Verboom, and
L Havekes
July 1990,
Biochemical and biophysical research communications,
H J Kempen, and
K van Son, and
L H Cohen, and
M Griffioen, and
H Verboom, and
L Havekes
January 1985,
Current topics in cellular regulation,
H J Kempen, and
K van Son, and
L H Cohen, and
M Griffioen, and
H Verboom, and
L Havekes
March 1989,
Journal of lipid research,
H J Kempen, and
K van Son, and
L H Cohen, and
M Griffioen, and
H Verboom, and
L Havekes
December 2005,
American journal of physiology. Endocrinology and metabolism,
H J Kempen, and
K van Son, and
L H Cohen, and
M Griffioen, and
H Verboom, and
L Havekes
January 2000,
Journal of atherosclerosis and thrombosis,
H J Kempen, and
K van Son, and
L H Cohen, and
M Griffioen, and
H Verboom, and
L Havekes
July 1992,
Biochimica et biophysica acta,
H J Kempen, and
K van Son, and
L H Cohen, and
M Griffioen, and
H Verboom, and
L Havekes
July 2003,
Kidney international,
