Choi P, Ostrerova-Golts N, Sparkman D, Cochran E, Lee J M, Wolozin B
Department of Pharmacology, Loyola University Medical Center, Maywood, IL 60153, USA.
Neuroreport. 2000 Aug 21;11(12):2635-8. doi: 10.1097/00001756-200008210-00006.
Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Immunostaining of substantia nigra sections from sporadic Parkinson's disease (PD) cases shows that Parkin accumulates in axonal spheroids and in some Lewy bodies. Because ubiquitin is a major component of Lewy bodies and axonal spheroids, we investigated whether Parkin is metabolized via the ubiquitin/proteosomal pathway. Treatment of BE-M17 neuroblastoma cells with the proteosomal inhibitor, MG132, produced a band corresponding to di-ubiquitinated Parkin that was apparent by immunoblot using two different anti-Parkin antibodies. This higher mol. wt band also co-immunoprecipitated with Parkin. These data suggest that Parkin plays a role in the pathophysiology of sporadic PD, and that Parkin is a substrate for ubiquitination that is degraded by the proteosomal complex.
帕金森病基因的突变会导致常染色体隐性少年帕金森病。对散发性帕金森病（PD）病例的黑质切片进行免疫染色显示，帕金森蛋白积聚在轴突球状体和一些路易小体中。由于泛素是路易小体和轴突球状体的主要成分，我们研究了帕金森蛋白是否通过泛素/蛋白酶体途径进行代谢。用蛋白酶体抑制剂MG132处理BE-M17神经母细胞瘤细胞，产生了一条与双泛素化帕金森蛋白相对应的条带，通过使用两种不同的抗帕金森蛋白抗体进行免疫印迹可明显看到该条带。这条分子量更高的条带也与帕金森蛋白进行了共免疫沉淀。这些数据表明，帕金森蛋白在散发性PD的病理生理学中起作用，并且帕金森蛋白是泛素化的底物，可被蛋白酶体复合物降解。
