Gene expression profile following stable expression of the cellular prion protein
Gene expression profile following stable expression of the cellular prion protein
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DOI：
10.1007/s10571-004-6920-0
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发表时间：
2004-12-01
影响因子：
4
通讯作者：
Yamamura, T
中科院分区：
文献类型：
--
作者：
Satoh, J;Yamamura, T
1. 细胞朊病毒蛋白（PrPC）在神经和非神经组织中广泛表达，在中枢神经系统（CNS）的神经元中表达水平最高。最近的研究表明，PrPC细胞质积累的转基因小鼠在小脑中表现出广泛的神经变性，尽管其潜在的机制尚不清楚。为了鉴定人类细胞中受PrPC过表达控制的基因，我们利用位点特异性重组技术建立了一株稳定表达PrPC的HEK293细胞系，命名为P1。微阵列分析发现，在检测的12814个基因中，有33个基因在P1与亲本prpc -不表达细胞系之间表达差异。其中18个基因与神经元和神经胶质功能有关，5个与细胞外基质蛋白的产生有关，2个位于补体级联中。Northern blot分析证实了脑特异性蛋白磷酸酶2A β亚基（PPP2R2B）的P1显著上调，PPP2R2B是脊髓小脑性共济失调的致病基因12，而小脑变性相关自身抗原（CDR34）基因与副肿瘤小脑变性的发生有关。这些结果表明，PrPC在细胞中的积累导致了对特定神经元功能重要的一系列基因的异常调节。这代表了prpc介导的选择性神经变性的可能机制。
1. The cellular prion protein (PrPC) is expressed widely in neural and nonneural tissues at the highest level in neurons in the central nervous system (CNS).2. Recent studies indicated that transgenic mice with the cytoplasmic accumulation of PrPC exhibited extensive neurodegeneration in the cerebellum, although the underlying mechanism remains unknown. To identify the genes whose expression is controlled by overexpression of PrPC in human cells, we have established a stable PrPC-expressing HEK293 cell line designated P1 by the site-specific recombination technique.3. Microarray analysis identified 33 genes expressed differentially between P1 and the parent PrPC-non-expressing cell line among 12,814 genes examined. They included 18 genes involved in neuronal and glial functions, 5 related to production of extracellular matrix proteins, and 2 located in the complement cascade.4. Northern blot analysis verified marked upregulation in P1 of the brain-specific protein phosphatase 2A beta subunit (PPP2R2B), a causative gene of spinocerebellar ataxia 12, and the cerebellar degeneration-related autoantigen (CDR34) gene associated with development of paraneoplastic cerebellar degeneration.5. These results indicate that accumulation of PrPC in the cell caused aberrant regulation of a battery of the genes important for specific neuronal function. This represents a possible mechanism underlying PrPC-mediated selective neurodegeneration.