N. Garcia-roman et al., Lovastatin induces apoptosis of spontaneously immortalized rat brain neuroblasts: Involvement of nonsterol isoprenoid biosynthesis inhibition, MOL CELL NE, 17(2), 2001, pp. 329-341
We have examined the effects of lovastatin and pravastatin (competitive HMG
-CoA reductase inhibitors) on the growth and survival of rat brain neurobla
sts. Lovastatin, but not pravastatin, suppressed cell growth by inducing ap
optosis of neuroblasts in a dose- and time-dependent manner. Apoptosis was
accompanied by a decrease in both Bcl-2 and Bcl-xL protein levels, suggesti
ng that changes in the expression of these genes may contribute to apoptosi
s following lovastatin treatment. Lovastatin treatment was also associated
with decreased prenylation of both Ras and Rho A proteins whereas Rac 1 ger
anylgeranylation was not affected. Lovastatin effects were fully prevented
by mevalonate. The present data suggest that lovastatin induces apoptosis o
f rat brain neuroblasts by its capacity to decrease the prenylation of spec
ific proteins involved in signal transduction pathways that control growth
and survival of neuronal cells.