The Identification and Characterization of Oxidized RNAs in Alzheimer's Disease

It has been shown that cytoplasmic RNA oxidation occurs to a great extent in the brains of Alzheimer's disease (AD) patients. The goal of this study was to isolate and identify oxidized RNA species in AD. We show that significant amounts of poly(A)+ mRNAs are oxidized in AD brains. RNA oxidatio...

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Bibliographic Details
Published in:The Journal of neuroscience 2003-06, Vol.23 (12), p.4913-4921
Main Authors: Shan, Xiu, Tashiro, Hirofumi, Lin, Chien-liang Glenn
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Alzheimer Disease - genetics
Alzheimer Disease - metabolism
Amyotrophic Lateral Sclerosis - genetics
Amyotrophic Lateral Sclerosis - metabolism
Animals
Cellular/Molecular
Clone Cells
Frontal Lobe - chemistry
Frontal Lobe - metabolism
Green Fluorescent Proteins
Humans
Luciferases - biosynthesis
Luciferases - genetics
Luminescent Proteins - biosynthesis
Luminescent Proteins - genetics
Middle Aged
Oligonucleotide Array Sequence Analysis
Oxidants - chemistry
Oxidants - pharmacology
Oxidation-Reduction
PC12 Cells
Poly A - chemistry
Poly A - metabolism
Precipitin Tests
Protein Biosynthesis
Protein Transport - drug effects
Rats
Reverse Transcriptase Polymerase Chain Reaction
RNA - chemistry
RNA - drug effects
RNA - metabolism
Transfection
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Summary:It has been shown that cytoplasmic RNA oxidation occurs to a great extent in the brains of Alzheimer's disease (AD) patients. The goal of this study was to isolate and identify oxidized RNA species in AD. We show that significant amounts of poly(A)+ mRNAs are oxidized in AD brains. RNA oxidation is not random but highly selective. Importantly, many identified oxidized mRNA species have been implicated in the pathogenesis of AD. Quantitative analysis revealed that some mRNA species are more susceptible to oxidative damage. We also investigated the biological consequence of oxidatively damaged mRNAs by expressing them in cell lines. Our data indicated that abnormal processing of proteins occurred to the oxidized mRNAs. This may implicate the potential contribution of RNA oxidation in the pathogenesis of AD.
ISSN:0270-6474
1529-2401
DOI:10.1523/jneurosci.23-12-04913.2003