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Messenger RNA oxidation is an early event preceding cell death and causes reduced protein expression
Author(s) -
Shan Xiu,
Chang Yueming,
Glenn Lin Chienliang
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.07-8200com
Subject(s) - rna , neurodegeneration , messenger rna , polysome , programmed cell death , microbiology and biotechnology , oxidative stress , biology , gene expression , protein biosynthesis , nuclease protection assay , reactive oxygen species , biochemistry , chemistry , ribosome , gene , non coding rna , apoptosis , medicine , disease
We previously reported that up to 50% of messenger RNAs (mRNA) are oxidatively damaged in the affected area of Alzheimer's disease (AD) brains. The role of RNA oxidation in the cell death process is unknown. In the present study, we used cortical primary dissociated cultures to investigate the relationship between RNA oxidation and neuron degeneration induced by various insults, including hydrogen peroxide, glutamate, and amyloid β peptide. These insults mediate the production of reactive oxygen species and thus induce oxidative stress. The results showed that RNA oxidation was an early event far preceding cell death, not merely a consequence of dying cells. RNA oxidation occurred primarily in a distinct group of neurons that died later. Identification of oxidized RNA species revealed that significant amounts of mRNAs were oxidized and that some mRNA species were more susceptible to oxidative damage, consistent with findings in the AD brain. The level of protein corresponding to the oxidized mRNA species was significantly decreased. Polyribosome analysis indicated that oxidized bases in mRNAs caused ribosome stalling on the transcripts, which led to a decrease of protein expression. These results suggest that RNA oxidation may be directly associated with neuronal deterioration, rather than harmless epiphenomenona, during the process of neu‐rodegeneration.—Shan X., Chang, Y., Lin C‐l. G. Messenger RNA oxidation is an early event preceding cell death and causes reduced protein expression. FASEB J. 21, 2753–2764 (2007)