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

FEBS Letters

Moratilla, Carmen¹  Renart, Jaime¹  López-Maderuelo, M.Dolores¹  Fernández-Renart, Margarita¹ 

[1] Instituto de Investigaciones Biomédicas ‘Alberto Sols’ CSIC-UAM, Arturo Duperier, 4, 28029 Madrid, Spain

关键词: Geldanamycin;    Raf-1;    Mitogen-activated protein kinase;    Apoptosis;    Differentiation;    ERK;    extracellular signal-regulated kinase;    GA;    Geldanamycin;    JNK;    c-jun N-terminal kinase;    MAPK;    mitogen-activated protein kinase;    MBP;    myelin basic protein;    NGF;    nerve growth factor;    PI3K;    phosphatidylinositol-3′-kinase;    PP2;    4-amino-5-(4-chlorophenyl)-7-(tbutyl)pyrazolo[3;    4-d]pyrimidine;   

DOI  :  10.1016/S0014-5793(01)02130-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown