Shen Aiguo, Chen Mengling, Niu Shuqiong, Sun Linlin, Gao Shangfeng, Shi Shuxian, Li Xin, Lv Qingshan, Guo Zhiqin, Cheng Chun
The Jiangsu Province Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, People's Republic of China.
J Chem Neuroanat. 2008 Jan;35(1):85-93. doi: 10.1016/j.jchemneu.2007.07.004. Epub 2007 Jul 31.
Peripheral nerve transection has been implicated to cause a production of neuronal nitric oxide synthase (nNOS), which may influence a range of post-axotomy processes necessary for neuronal survival and nerve regeneration. Carboxy-terminal post synaptic density protein/Drosophila disc large tumor suppressor/zonula occuldens-1 protein (PDZ) ligand of neuronal nitric oxide synthase (CAPON), as an adaptor, interacts with nNOS via the PDZ domain helping regulate nNOS activity at postsynaptic sites in neurons. And Dexras1, a small G protein mediating multiple signal transductions, has been reported to form a complex with CAPON and nNOS. A role for the physiologic linkage by CAPON of nNOS to Dexras1 has suggested that NO-mediated activation of Dexras1 is markedly enhanced by CAPON. We investigated the changes in mRNA for CAPON, Dexras1 and nNOS in the sciatic nerve, dorsal root ganglia and lumbar spinal cord of adult rat following sciatic axotomy by TaqMan quantitative real-time PCR and in situ hybridization combined with immunofluorescence. Signals of mRNA for CAPON and Dexras1 were initially expressed in these neural tissues mentioned, transiently increased at certain time periods after sciatic axotomy and finally recovered to the basal level. It was also found that nNOS mRNA underwent a similar change pattern during this process. These results suggest that CAPON as well as Dexras1 may be involved in the different pathological conditions including nerve regeneration, neuron loss or survival and even pain process, possibly via regulating the nNOS activity or through the downstream targets of Dexras1.
外周神经横断已被认为会导致神经元型一氧化氮合酶(nNOS)的产生,这可能会影响一系列对于神经元存活和神经再生所必需的轴突切断后过程。神经元型一氧化氮合酶的羧基末端突触后致密蛋白/果蝇盘大肿瘤抑制因子/紧密连接蛋白1(CAPON)作为衔接蛋白,通过PDZ结构域与nNOS相互作用,有助于调节神经元突触后位点的nNOS活性。并且,已报道小G蛋白Dexras1介导多种信号转导,它可与CAPON和nNOS形成复合物。CAPON将nNOS与Dexras1进行生理连接的作用表明,CAPON可显著增强NO介导的Dexras1激活。我们通过TaqMan定量实时PCR以及结合免疫荧光的原位杂交技术,研究了成年大鼠坐骨神经切断后坐骨神经、背根神经节和腰脊髓中CAPON、Dexras1和nNOS的mRNA变化。CAPON和Dexras1的mRNA信号最初在上述神经组织中表达,在坐骨神经切断后的特定时间段内短暂增加,最终恢复到基础水平。在此过程中还发现nNOS mRNA呈现类似的变化模式。这些结果表明,CAPON以及Dexras1可能通过调节nNOS活性或通过Dexras1的下游靶点,参与包括神经再生、神经元丢失或存活甚至疼痛过程在内的不同病理状况。