Opposite effects of the Hsp90 inhibitor Geldanamycin:: induction of apoptosis in PC12, and differentiation in N2A cells
Opposite effects of the Hsp90 inhibitor Geldanamycin:: induction of apoptosis in PC12, and differentiation in N2A cells
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DOI：
10.1016/s0014-5793(01)02130-5
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发表时间：
2001-02-09
期刊：
影响因子：
3.5
通讯作者：
Renart, J
中科院分区：
文献类型：
--
作者：
López-Maderuelo, MD;Fernández-Renart, M;Renart, J
据报道，Hsp90伴侣格尔达霉素的抑制剂具有多种细胞效应，如抑制v-src活性或破坏Raf-1的稳定等。我们现在表明，格尔达霉素在不同细胞系中诱导不同的表型。在PC12细胞中，它触发凋亡，而在小鼠神经母细胞瘤N2A中，它诱导分化并产生神经突，格尔达霉素的作用不能通过抑制c-src蛋白酪氨酸激酶来模仿，神经生长因子不能保护PC12细胞免于凋亡，丝裂原激活的蛋白激酶活性ERK和JNK根据细胞类型的不同而被激活：在PC12细胞中，JNK被激活，其抑制能消除凋亡，而ERK则不能；在N2A细胞中，ERK和JNK都被激活，但在不同的时间达到峰值。(C) 2001欧洲生化学会联合会，Elsevier Science B.V.出版，版权所有。
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. (C) 2001 Federation of European Biochemical Societies, Published by Elsevier Science B.V. All rights reserved.