Neurite outgrowth of NG108-15 cells induced by heat shock protein 90 inhibitors.
We previously reported that radicicol (Rad) and geldanamycin (Geld), heat shock protein 90 (Hsp90) inhibitors, potentiate neurite growth of cultured sensory neurons from chick embryo. We now show that the antibiotics induce neurite growth in NG108-15 cells. Treatment of the cells with these drugs caused transient decrease in protein levels of Raf1, ERK1/2, phosphorylated ERK1/2, Akt1, and CDK4. The neurite growth of NG108-15 induced by the inhibitors was blocked by actynomycin D, but the neurite growth stimulated by dbcAMP in the cells was not affected. The neurite growth could be due to a change in the synthesis of some specific protein(s) and is speculated to be due to the transient downregulation of particular-signaling molecules stabilized by Hsp90.
Jin
Erika
E
Department of Biology, Kyoto Prefectural University of Medicine, Kyoto 603-8334, Japan.
Sano
Mamoru
M
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D018942:Macrolides / Q000494:pharmacology; D051379:Mice; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D016227:Benzoquinones; D004791:Enzyme Inhibitors; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D018942:Macrolides; D003609:Dactinomycin; D020932:Nerve Growth Factor; D000242:Cyclic AMP; C035359:monorden; C001277:geldanamycin