Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adult
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Aged
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Aged, 80 and over
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Alzheimer Disease / genetics*
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Alzheimer Disease / metabolism*
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Amyotrophic Lateral Sclerosis / genetics
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Amyotrophic Lateral Sclerosis / metabolism
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Animals
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Clone Cells
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Frontal Lobe / chemistry
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Frontal Lobe / metabolism
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Green Fluorescent Proteins
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Humans
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Luciferases / biosynthesis
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Luciferases / genetics
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Luminescent Proteins / biosynthesis
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Luminescent Proteins / genetics
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Middle Aged
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Oligonucleotide Array Sequence Analysis
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Oxidants / chemistry
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Oxidants / pharmacology
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Oxidation-Reduction
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PC12 Cells
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Poly A / chemistry
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Poly A / metabolism
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Precipitin Tests
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Protein Biosynthesis
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Protein Transport / drug effects
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RNA / chemistry
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RNA / drug effects
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RNA / metabolism*
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Rats
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Reverse Transcriptase Polymerase Chain Reaction
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Transfection
Substances
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Luminescent Proteins
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Oxidants
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Green Fluorescent Proteins
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Poly A
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RNA
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Luciferases