Quantification of oxidized RNAs in Alzheimer's disease.
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.
Shan
Xiu
X
Department of Neuroscience, The Ohio State University, 4198 Graves Hall, 333 West 10th Avenue, Columbus, OH 43210, USA.
Lin
Chien-Liang Glenn
CL
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D015139:Blotting, Southern; D001923:Brain Chemistry / Q000502:physiology*; D018076:DNA, Complementary / Q000096:biosynthesis; D005260:Female; D005625:Frontal Lobe / Q000737:chemistry; D006151:Guanosine / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D010084:Oxidation-Reduction; D011061:Poly A / Q000032:analysis; D012313:RNA / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018076:DNA, Complementary; D006151:Guanosine; D011061:Poly A; C046215:8-hydroxyguanosine; D012313:RNA