Lee H G, Park S J, Choi E K, Carp R I, Kim Y S
Institute of Environment & Life Science, Hallym Academy of Sciences, Chuncheon, Korea.
J Mol Neurosci. 1999 Aug-Oct;13(1-2):121-6. doi: 10.1385/JMN:13:1-2:121.
Prion diseases of humans and animals occur following infection with infectious agents containing PrP(Sc) or in situations in which there is a mutation of the prion protein (PrP) gene. The cellular prion protein (PrP(C)) is a sialoglycoprotein that is expressed predominantly in neurons. PrP(C) is converted into a pathogenic form of PrP (PrP(Sc)), which is distinguishable from PrP(C) by its relative resistance to protease digestion. A number of postulates have been advanced for the function of normal PrP (PrP(C)), but this issue has not been resolved. To investigate the function(s) of PrP(C), we established clonal PC12 cell lines, which have elevated PrP(C) expression. The results show that there were alterations in dopamine metabolism and in monoamine oxidase (MAO) activity in transfected PC12 cells that overexpress PrP(C). There was an increase in concentration of DOPAC, a metabolite of dopamine, and in MAO activity in cells overexpressing PrP(C). MAO is involved in oxidative degradation of dopamine (DA). Our data suggest that PrP(C) plays a role in DA metabolism by regulating MAO activity.
人类和动物的朊病毒疾病在感染含有PrP(Sc)的感染性因子后发生，或在朊病毒蛋白（PrP）基因发生突变的情况下发生。细胞朊病毒蛋白（PrP(C)）是一种主要在神经元中表达的唾液酸糖蛋白。PrP(C)转化为致病性PrP形式（PrP(Sc)），后者因其对蛋白酶消化的相对抗性而与PrP(C)区分开来。关于正常PrP（PrP(C)）的功能已经提出了许多假设，但这个问题尚未得到解决。为了研究PrP(C)的功能，我们建立了PrP(C)表达升高的克隆PC12细胞系。结果表明，在过表达PrP(C)的转染PC12细胞中，多巴胺代谢和单胺氧化酶（MAO）活性发生了改变。在过表达PrP(C)的细胞中，多巴胺的代谢产物3,4-二羟基苯乙酸（DOPAC）浓度增加，MAO活性增加。MAO参与多巴胺（DA）的氧化降解。我们的数据表明，PrP(C)通过调节MAO活性在DA代谢中起作用。
