Time response of cholesterol synthesis inhibition by compactin-related compounds. In vitro quantitation of the "escape phenomenon".
The time course of the inhibition of cholesterol synthesis by low and high doses of mevinolin and monacolin X were studied in normal human skin fibroblasts, fibroblasts without low density lipoprotein receptor and HepG2 hepatoma cells. Low doses of the inhibitors (0.2 ng/mL) caused a sharp decrease in the rate of cholesterol synthesis during the first 2-3 h, which gradually increased to about 40% during the next 6 h. Further incubation led to a decrease or stabilization of the cholesterol synthesis rate. High doses of the drugs (100 mg/mL) strongly inhibited cholesterol synthesis during the first 2-3 h, followed by a moderate increase during the next 20 h. No drug or tissue selectivity was observed.
Sviridov
D D
DD
Institute of Experimental Cardiology, Cardiology Research Center, Moscow, Russia.
Endo
A
A
Pavlov
M Y
MY
Repin
V S
VS
D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002784:Cholesterol / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000378:metabolism; D008148:Lovastatin / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D012867:Skin / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000924:Anticholesteremic Agents; D009281:Naphthalenes; C045374:monacolin X; D002784:Cholesterol; D008148:Lovastatin