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首页> 外文期刊>The European Journal of Neuroscience >A natural antisense transcript against Rad18, specifically expressed in neurons and upregulated during beta-amyloid-induced apoptosis.
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A natural antisense transcript against Rad18, specifically expressed in neurons and upregulated during beta-amyloid-induced apoptosis.

机译:Rad18的天然反义转录物,特别是在神经元中表达,并在β-淀粉样蛋白诱导的细胞凋亡期间被上调。

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摘要

Apoptosis, the main form of programmed cell death, is associated to a complex and dynamic transcriptional and post-transcriptional programme. By microarray analysis, we have previously implicated 241 genes differentially expressed in rat cortical neurons exposed to beta-amyloid (Abeta) protein, the major constituent of amyloid plaques in Alzheimer's disease. A large number of identified genes have no name or known function. In the present study, we have investigated one of these genes that encodes for a natural antisense transcript against Rad18 (NAT-Rad18). Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) confirmed differential expression of this transcript in cortical neurons exposed to Abeta. In situ hybridization, qRT-PCR and immunohistochemistry were used to assess the regional and cellular distribution of NAT-Rad18 in adult rat brain. These experiments showed a widespread distribution of NAT-Rad18, with the highest levels in the cerebellum, brainstem and cortex, where it was specifically expressed by neurons. NAT-Rad18 was also strongly expressed in epithelial cells of choroid plexus and cerebral vessels. At the cellular level, expression of Rad18 was counterbalanced by that of its natural antisense transcript, as shown by both in situ hybridization and immunohistochemistry. These experiments suggest the existence of a NAT that exerts a post-transcriptional control over Rad18.
机译:细胞凋亡是程序性细胞死亡的主要形式,它与复杂而动态的转录和转录后程序有关。通过微阵列分析,我们以前牵涉到暴露于β-淀粉样蛋白(Abeta)蛋白(在阿尔茨海默氏病中淀粉样斑块的主要成分)的大鼠皮质神经元中差异表达的241个基因。大量已鉴定的基因没有名称或已知功能。在本研究中,我们研究了这些基因之一,该基因编码针对Rad18的天然反义转录本(NAT-Rad18)。实时定量逆转录聚合酶链反应(qRT-PCR)证实了该转录本在暴露于Abeta的皮质神经元中的差异表达。原位杂交,qRT-PCR和免疫组化被用来评估成年大鼠脑中NAT-Rad18的区域和细胞分布。这些实验显示了NAT-Rad18的广泛分布,在小脑,脑干和皮质中的含量最高,而NAT-Rad18在神经元中特异性表达。 NAT-Rad18在脉络丛和脑血管的上皮细胞中也强烈表达。在细胞水平上,Rad18的表达与其天然反义转录物的表达平衡,如原位杂交和免疫组织化学所显示。这些实验表明存在对Rad18进行转录后控制的NAT。

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