The activation of the ERK pathway contributes to the spinal c-fos expression observed after noxious bladder stimulation
The activation of the ERK pathway contributes to the spinal c-fos expression observed after noxious bladder stimulation
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DOI：
10.1080/08990220601143265
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发表时间：
2007-01-01
影响因子：
0.9
通讯作者：
Cruz, Francisco
中科院分区：
文献类型：
--
作者：
Cruz, Celia D.;Ferreira, Daniel;Cruz, Francisco
C-fos是一种即早基因，其在脊髓中的表达已被广泛用作外周伤害性刺激的标志物。Fos蛋白在脊髓神经元的细胞核中积累，在刺激后2小时达到可检测的水平。ERK信号通路是脊髓神经元的重要信号通路。ERK在特定氨基酸残基上磷酸化后被激活。它在脊髓中的激活，伤害性刺激后，已被证明有助于建立和维持与慢性疼痛相关的长期神经元改变。磷酸化ERK可以靶向包括转录因子在内的多种细胞元件，这表明ERK参与基因表达的调控。ERK与c-fos的关系目前尚不清楚。一些体外研究已经得出结论，ERK有助于c-fos的调节，而另一些人则提供了ERK非依赖性c-fos表达的证据。事实上，在脊髓中，已经报道了在没有ERK磷酸化的情况下c-fos表达的发生。在这项研究中，我们调查了在体内的ERK的c-fos在脊髓表达的贡献。通过鞘内给予PD 98059抑制脊髓ERK激活，我们证实ERK磷酸化确实有助于调节膀胱伤害性刺激后c-fos表达。
C-fos is an immediate-early gene whose expression in the spinal cord has been extensively used as a marker of peripheral noxious stimulation. The Fos protein accumulates in the nuclei of spinal neurons, reaching detectable levels 2 h after stimulation. The ERK pathway is an important signalling pathway in spinal cord neurons. ERK is activated upon phosphorylation on specific amino acid residues. Its activation in the spinal cord, following noxious stimulation, has been shown to contribute to the establishment and maintenance of long-term neuronal alterations associated with chronic pain. Phosphorylated ERK can target several cellular elements, including transcription factors, which indicates that ERK participates in the regulation of gene expression. The relation between ERK and c-fos is at present still unclear. Some in vitro studies have reached the conclusion that ERK contributes to c-fos regulation whereas others have provided evidence of ERK-independent c-fos expression. In fact, in the spinal cord the occurrence of c-fos expression in the absence of ERK phosphorylation has been reported. In this study we investigated in vivo the contribution of ERK to c-fos expression in the spinal cord. By inhibiting spinal ERK activation with intrathecal administration of PD98059, we verified that ERK phosphorylation does contribute to regulate c-fos expression upon noxious bladder stimulation.