Blocked MAP kinase activity selectively enhances neurotrophic growth responses
Blocked MAP kinase activity selectively enhances neurotrophic growth responses
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DOI：
10.1016/j.mcn.2003.10.015
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发表时间：
2004-02-01
影响因子：
3.5
通讯作者：
Ebendal, T
中科院分区：
文献类型：
--
作者：
Althini, S;Usoskin, D;Ebendal, T
骨形态发生蛋白（BMP）4和6以及MEK抑制剂PD 98059和U 0126增强神经营养因子3（NT 3）和neurturin（NTN）诱导的E9鸡胚外周神经元的轴突生长和存活。预暴露于BMP 4或PD 98059足以引发随后添加的NT 3的增强作用。由NT 3诱导的Erk 2磷酸化通过MEK抑制而减少，但不受BMP信号传导的影响。实时PCR显示，无论是BMP刺激还是MEK抑制都不会增加Trk受体的表达，并且BMP诱导的基因Smad 6和Id 1不会被PD 98059上调。相反，MEK抑制和BMP信号传导抑制血清反应元件（SRE）驱动的Egr 1基因的转录。使用NGF刺激的PC 12细胞的报告基因测定表明，MEK/Erk/Elk驱动的转录活性被Smad 1/5和PD 98059抑制。因此，抑制SRE控制的转录代表了调节神经营养反应的途径的一个可能的汇合点。(C)2004年爱思唯尔公司All rights reserved.
Bone morphogenetic proteins (BMPs) 4 and 6 as well as MEK inhibitors PD98059 and U0126 potentiate neurotrophin 3 (NT3)- and neurturin (NTN)-induced neurite outgrowth and survival of peripheral neurons from the E9 chicken embryo. Preexposure to BMP4 or PD98059 was sufficient to prime the potentiation of subsequently added NT3. Phosphorylation of Erk2, induced by NT3, was reduced by MEK inhibition but unaffected by BMP signaling. Real-time PCR showed that neither BMP stimulation nor MEK inhibition increased Trk receptor expression and that the BMP-induced genes Smad6 and Id1 were not upregulated by PD98059. In contrast, both MEK inhibition and BMP signaling suppressed transcription of the serum-response element (SRE)-driven Egr1 gene. A reporter assay using NGF-stimulated PC12 cells demonstrated that MEK/Erk/Elk-driven transcriptional activity was inhibited by Smad1/5 and by PD98059. Thus, suppression of SRE-controlled transcription represents a likely convergence point for pathways regulating neurotrophic responses. (C) 2004 Elsevier Inc. All rights reserved.