Shan Xiu, Lin Chien-Liang Glenn
Department of Neuroscience, The Ohio State University, 4198 Graves Hall, 333 West 10th Avenue, Columbus, OH 43210, USA.
Neurobiol Aging. 2006 May;27(5):657-62. doi: 10.1016/j.neurobiolaging.2005.03.022. Epub 2005 Jun 24.
Cytoplasmic RNA oxidation is a prominent feature of vulnerable neurons in the brains of Alzheimer's disease (AD) patients. We previously demonstrated that messenger RNAs (mRNA) are oxidized in AD brains. However, the magnitude of the mRNA oxidation is unclear. In the present study, we separated oxidized mRNAs from non-oxidized mRNAs by immunoprecipitation and then quantitatively analyzed both mRNA fractions. Surprisingly, 30-70% of the mRNAs isolated from AD frontal cortices were oxidized while the abundance of oxidized mRNAs was low in age-matched normal controls. Furthermore, we previously showed that some mRNA species are more susceptible to oxidative damage. Here, we quantified the degree of oxidation for individual mRNA species that were previously found to be oxidized in AD. Quantitative analysis revealed that the relative amounts of oxidized transcripts reach 50-70% for some mRNA species. These high abundances implicate the potential contribution of mRNA oxidation to the pathogenesis of AD.
细胞质RNA氧化是阿尔茨海默病（AD）患者大脑中易损神经元的一个显著特征。我们之前证明了信使RNA（mRNA）在AD大脑中会被氧化。然而，mRNA氧化的程度尚不清楚。在本研究中，我们通过免疫沉淀从未氧化的mRNA中分离出氧化的mRNA，然后对这两种mRNA组分进行定量分析。令人惊讶的是，从AD额叶皮质分离出的mRNA中有30 - 70%被氧化，而在年龄匹配的正常对照中氧化mRNA的丰度较低。此外，我们之前表明某些mRNA种类更容易受到氧化损伤。在这里，我们对之前发现在AD中被氧化的单个mRNA种类的氧化程度进行了定量。定量分析表明，对于某些mRNA种类，氧化转录本的相对量达到50 - 70%。这些高丰度表明mRNA氧化对AD发病机制可能有贡献。
