3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitor impairs cell p4fferentiation in cultured adipogenic cells (3T3-L1).
Lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, inhibits the synthesis of mevalonic acid. We examined the effect of lovastatin on the differentiation of the fibroblast/adipocyte cell line (3T3-L1). Lovastatin inhibits the differentiation of 3T3-L1 cells in a dose-dependent fashion. The inhibitory effect of lovastatin was partially reversed by adding exogenous mevalonic acid to the 3T3-L1 cells. Exogenous cholesterol (15 micrograms/ml) did not prevent lovastatin inhibition of adipocyte conversion. The isoprenoids, farnesol and geraniol, partially prevented lovastatin inhibition of adipocyte conversion but squalene did not prevent lovastatin inhibition of adipocyte conversion. We conclude that the inhibitory effect of lovastatin was partially due to the blockade of the pathway leading to synthesis of isoprenoids, which are downstream products of mevalonic acid.
Nishio
E
E
Department of Pharmacology, National Defense Medical College, Japan.
Tomiyama
K
K
Nakata
H
H
Watanabe
Y
Y
D016475:3T3 Cells; D000080462:Acyclic Monoterpenes; D000818:Animals; D001391:Azo Compounds; D002454:Cell Differentiation / Q000187:drug effects; D002784:Cholesterol / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005204:Farnesol / Q000494:pharmacology; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D050356:Lipid Metabolism; D008148:Lovastatin / Q000494:pharmacology*; D008798:Mevalonic Acid / Q000494:pharmacology; D051379:Mice; D013729:Terpenes / Q000494:pharmacology
D000080462:Acyclic Monoterpenes; D001391:Azo Compounds; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013729:Terpenes; D005204:Farnesol; D002784:Cholesterol; D008148:Lovastatin; D005993:Glycerolphosphate Dehydrogenase; C011049:oil red O; C007836:geraniol; D008798:Mevalonic Acid