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Opposite effects of the Hsp90 inhibitor Geldanamycin: induction of apoptosis in PC12, and differentiation in N2A cells
Author(s) -
López-Maderuelo M.Dolores,
Fernández-Renart Margarita,
Moratilla Carmen,
Renart Jaime
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02130-5
Subject(s) - geldanamycin , microbiology and biotechnology , hsp90 , mapk/erk pathway , apoptosis , kinase , tyrosine kinase , chemistry , p38 mitogen activated protein kinases , biology , signal transduction , heat shock protein , biochemistry , gene
The inhibitor of the Hsp90 chaperone Geldanamycin has been reported to have several cellular effects, such as inhibition of v‐src activity or destabilization of Raf‐1 among others. We show now that Geldanamycin treatment induces different phenotypes in different cell lines. In PC12 cells, it triggers apoptosis, whereas in the murine neuroblastoma N2A, it induces differentiation with neurite outgrowth. Geldanamycin effects cannot be mimicked by inhibition of the c‐src protein tyrosine kinases, and nerve growth factor does not protect PC12 cells from apoptosis. Mitogen‐activated protein kinase activities ERK and JNK are activated differently according to cell type: in PC12 cells JNK is activated, and its inhibition abolishes apoptosis, but not ERK; in N2A cells, both ERK and JNK are activated, but with peak activities at different times.