Simvastatin inhibits the division and induces neurite-like outgrowth in PC12 cells.
Simvastatin, a potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. inhibited cell division in a dose dependent fashion and induced neurite-like outgrowth in PC12 cells. The neurite-like outgrowth was detectable at 0.5 microg/ml of simvastatin 24 h after the treatment. The responses to simvastatin were completely prevented by incubating the cells with mevalonate. In contrast to simvastatin, pravastatin, a similar HMG-CoA reductase inhibitor but lipophobic, had no effect on the cells. The results provide new possibilities for the central nervous system (CNS) side effects of simvastatin therapy.
Sato-Suzuki
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Department of Physiological Chemistry, Graduate School, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Japan.
Murota
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D000214:Acyl Coenzyme A / Q000037:antagonists & inhibitors; D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008798:Mevalonic Acid / Q000494:pharmacology; D016501:Neurites / Q000502:physiology*; D016716:PC12 Cells; D017035:Pravastatin / Q000494:pharmacology; D051381:Rats; D019821:Simvastatin
D000214:Acyl Coenzyme A; D004791:Enzyme Inhibitors; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D008148:Lovastatin; D019821:Simvastatin; D017035:Pravastatin; D008798:Mevalonic Acid