Inhibition of cholesterol production but not of nonsterol isoprenoid products induces neuronal cell death.

摘要: Deficiency of nonsterol isoprenoids, intermediate metabolites the cholesterol biosynthetic pathway, has been known to cause an inhibition DNA synthesis and cell growth, induce apoptosis in nonneuronal cells. To investigate whether this is also case neurons, we examined effect a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor on viability neuronal cultures prepared from fetal rat brains. Treatment with compactin, competitive HMG-CoA reductase, induced death dose-dependent manner. Concurrent treatment cholesterol, beta-migrating very low density lipoprotein, mevalonate, or squalene substantially inhibited induction by compactin. Cell was squalestatin, which specifically inhibits biosynthesis at site downstream generation metabolites. Furthermore, squalestatin-induced concurrent incubation but not mevalonate. In contrast, growth proliferating cells such as NIH 3T3 PC12 exclusively dependent level isoprenoid products that cholesterol. The results study clearly indicate different cells, depends intracellular content products.