Mevalonate pathway and isoprenoids regulate human bronchial myocyte proliferation.
The role of mevalonate and geranylgeraniol in the control of cellular proliferation of cultured human bronchial myocytes was examined by investigating the effect of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme in mevalonate synthesis. Simvastatin inhibited the rate of growth of human bronchial smooth muscle cells in a concentration-dependent manner, with an IC50 value of 0.97 +/- 0.1 microM. Mevalonate (100 microM), as well as geranylgeraniol (5 microM), at their highest non-toxic concentrations, restored cell proliferation to control levels.
Viganõ
T
T
Institute of Pharmacological Sciences, University of Milan, Italy.
Hernandez
A
A
Corsini
A
A
Granata
A
A
Belloni
P
P
Fumagalli
R
R
Paoletti
R
R
Folco
G
G
D001980:Bronchi / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008168:Lung / Q000187:drug effects*; D008798:Mevalonic Acid / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects; D019821:Simvastatin
D004224:Diterpenes; D004791:Enzyme Inhibitors; D008148:Lovastatin; D019821:Simvastatin; C017338:geranylgeraniol; D008798:Mevalonic Acid