Increased levels of ubiquitin in the 6-OHDA-lesioned striatum of rats.
Increased levels of ubiquitin in the 6-OHDA-lesioned striatum of rats.
复制标题
大鼠 6-OHDA 损伤纹状体中泛素水平升高。
DOI：
10.1021/pr049836h
复制
发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Andren,PerE
中科院分区：
文献类型：
--
作者：
Pierson,Johan;Svenningsson,Per;Caprioli,RichardM;Andren,PerE
多种基因缺陷已将受损的泛素结合途径与各种常见形式的帕金森病联系起来。因此，我们研究了6-羟多巴胺（一种用于帕金森病实验模型的多巴胺能神经毒素）在引起蛋白质降解及其与泛素蛋白酶体系统的关联中的可能作用。使用单侧6-羟多巴胺去神经大鼠和直接在脑组织切片上的质谱分析，我们在这里首次报道了非共轭泛素水平的增加，特别是在多巴胺缺失半球的背纹状体。在完整的半球或多巴胺缺失半球的腹侧纹状体中没有发现类似的变化。纹状体多巴胺转运体结合强烈减少，表明多巴胺神经元大量丢失，证实了纹状体多巴胺神经支配的损伤。这些结果表明多巴胺神经元的去神经支配本身与泛素通路的调节有关，至少在帕金森病的经典动物模型中是这样。这项研究为泛素-蛋白酶体系统在帕金森病中的作用提供了更多的信息。关键词：帕金森病、谱分析、质谱分析、蛋白质组学、神经毒素、蛋白酶体、6-羟色胺、大鼠、MALDI、大脑
Multiple genetic deficits have linked impaired ubiquitin-conjugation pathways to various forms of familiar Parkinson's disease. We therefore examined the possible role of 6-hydroxydopamine, a dopaminergic neurotoxin used in Parkinson's disease experimental models, in causing protein degradation and its association with the ubiquitin proteasome system. Using unilaterally 6-hydroxydopamine-denervated rats and mass spectrometry profiling directly on brain tissue sections, we here report for the first time an increased level of unconjugated ubiquitin specifically in the dorsal striatum of the dopamine depleted hemisphere. No similar changes were found in the intact hemisphere or in the ventral striatum of the dopamine depleted hemisphere. The lesioning of the dopamine innervation to the striatum was confirmed by a strongly reduced dopamine transporter binding in the striatum, indicating an abundant loss of dopamine neurons. These results suggest that denervation of dopamine neurons per se is implicated in the regulation of ubiquitin pathways, at least in a classical animal model of Parkinson's disease. This study adds additional information regarding the involvement of the ubiquitin−proteasome system in Parkinson's disease.Keywords: Parkinson's disease • profiling mass spectrometry • proteomics • neurotoxin • proteasome • 6-OHDA • rat • MALDI • brain