Opposite effects of the Hsp90 inhibitor Geldanamycin: induction of apoptosis in PC12, and differentiation in N2A cells

The inhibitor of the Hsp90 chaperone Geldanamycin has been reported to have several cellular effects, such as inhibition of v-src activity or destabil ization of Raf-1 among others, We show now that Geldanamycin treatment indu ces different phenotypes in different cell lines. In PC12 cells, it trigger s apoptosis, whereas in the murine neuroblastoma N2A, it induces differenti ation with neurite outgrowth, Geldanamycin effects cannot be mimicked by in hibition of the c-src protein tyrosine kinases, and nerve growth factor doe s not protect PC12 cells from apoptosis, Mitogen-activated protein kinase a ctivities ERK and JNK are activated differently according to cell type: in PC12 cells JNK is activated, and its inhibition abolishes apoptosis, but no t ERK; in N2A cells, both ERK and JNK are activated, but with peak activiti es at different times. (C) 2001 Federation of European Biochemical Societie s, Published by Elsevier Science B.V. All rights reserved.