Fig. 4

Statins inhibit the ERK MAP kinase pathway in YT-INDY cells. YT-INDY cells were incubated with various concentration of statins, followed by Western blotting for ERK and phospho-ERK. Control cells were treated with the solvents in which the drugs were dissolved. All compounds were added to the cells at the start of the experiment. Each experiment was performed at least four times. a The results demonstrate that lovastatin, simvastatin, atorvastatin, mevastatin and fluvastatin could inhibit ERK MAP kinase pathway activation at relatively low drug concentrations, whereas no inhibition of the pathway was observed with pravastatin. This was likely due to the hydrophilic nature of the drug preventing it from crossing the YT-INDY cell membrane. b Using the five statins that inhibited the ERK MAP kinase pathway, the ability of mevalonate (1 mM or 0.5 mM) to restore the pathway was determined. Our results showed that 1 mM mevalonate was capable of restoring all statin-mediated inhibition of the ERK MAP pathway and 0.5 mM was sufficient to restore activity for all statins except lovastatin