Fibroblast growth factor 1 inhibits p53-dependent apoptosis in PC12 cells
Fibroblast growth factor 1 inhibits p53-dependent apoptosis in PC12 cells
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DOI：
10.1007/s10495-007-0072-x
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发表时间：
2007-08-01
期刊：
影响因子：
7.2
通讯作者：
Renaud, Flore
中科院分区：
文献类型：
--
作者：
Bouleau, Sylvina;Parvu-Ferecatu, Ioana;Renaud, Flore
在体外和(或)体内观察不同类型神经元在不同应激和不同退行性病变条件下FGF1的存活活性和P53的促凋亡活性。为了研究FGF1和P53通路在神经细胞中是否相互作用，我们研究了FGF1对P53依赖的PC12细胞凋亡的影响。我们首次表征了依托泊苷(一种DNA损伤剂)诱导的依赖于p53的PC12细胞死亡。我们发现依托泊苷增加了P53的稳定性、磷酸化(Ser-15)、核转位和转录活性。特别是，P53促进了PC12细胞MDM2、p21、PUMA和NOXA的表达。P53的激活启动了与caspase激活和核降解相关的经典的线粒体凋亡过程。我们证明，FGF1从线粒体和核事件的上游保护PC12细胞免受P53依赖的凋亡。FGF1抑制依托泊苷诱导的P53磷酸化、稳定化、核转位和转录活性。这项研究首次证明FGF1和P53通路在神经细胞中相互作用，并且FGF1保护神经细胞免受P53依赖的细胞凋亡，这表明FGF1/P53串扰的改变可能涉及广泛的神经元和神经疾病。
The survival activity of FGF1 and the pro-apoptotic activity of p53 were characterized in vitro and/or in vivo for different types of neurons after different stresses and in different neurodegenerative pathologies. To investigate whether or not FGF1 and p53 pathways interact in neuronal cells, we studied the effect of FGF1 on p53-dependent apoptosis in PC12 cells. We first characterized p53-dependent PC12 cell death induced by etoposide (a DNA damaging agent). We showed that etoposide increased p53 stabilization, phosphorylation (Ser-15), nuclear translocation and transcriptional activity. In particular, p53 promoted mdm2, p21, puma and noxa expression in PC12 cells. The activation of p53 initiated a classical mitochondrial apoptosis process associated with caspases activation and nuclear degradation. We demonstrated that FGF1 protected PC12 cells from p53-dependent apoptosis upstream from mitochondrial and nuclear events. FGF1 inhibited etoposide-induced p53 phosphorylation, stabilization, nuclear translocation and transcriptional activity. This study presents the first evidence that FGF1 and p53 pathways interact in neuronal cells, and that FGF1 protects neuronal cells from p53-dependent apoptosis, suggesting that alterations of FGF1/p53 crosstalk could be involved in a large range of neurons and in neurological disorders.