Hydrogen peroxide causes greater oxidation in cellular RNA than in DNA

Abstract

Human A549 lung epithelial cells were challenged with 18O-labeled hydrogen peroxide ([18O]-H2O2), the total RNA and DNA extracted in parallel, and analyzed for 18O-labeled 8-oxo-7,8-dihydroguanosine ([18O]-8-oxoGuo) and 8-oxo-7,8-dihydro-2'-deoxyguanosine ([18O]-8-oxodGuo) respectively, using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-MS/MS). [18O]-H2O2 exposure resulted in dose-response formation of both [18O]-8-oxoGuo and [18O]-8-oxodGuo and 18O-labeling of guanine in RNA was 14-25 times more common than in DNA. Kinetics of formation and subsequent removal of oxidized nucleic acids adducts were also monitored up to 24 h. The A549 showed slow turnover rates of adducts in RNA and DNA giving half-lives of approximately 12.5 h for [18O]-8-oxoGuo in RNA and 20.7 h for [18O]-8-oxodGuo in DNA, respectively.

Nucleic acid oxidation in Alzheimer disease

“…This is a reasonable proposition given also the relative cellular abundance of RNA and the subcellular distribution of RNA that locates in the vicinity of the source of ROS, mitochondria [9]. Indeed, greater oxidation in RNA than in DNA was demonstrated in several experimental studies on isolated DNA and RNA [140] as well as on nonneuronal cell lines and tissue, namely, human leukocytes [141], human skin fibroblasts [142], and human lung epithelial cells [143].…”

Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases

“…The RNA is more prone to oxidative damage than DNA, due to its single stranded nature, lack of an active repair mechanism for oxidized RNA, less protection by proteins than DNA and moreover these cytoplasmic RNAs are located in close proximity to the mitochondria where loads of ROS are produced. Indeed, RNA is subjected to more oxidative damage than DNA in humans [77]. 7, 8-dihydro-8-oxoguanosine (8-oxoG) is the most extensively studied RNA damage product and its levels are raised in various pathological conditions like Alzheimer's disease [78], Parkinson's disease [79], atherosclerosis [80], hemochromastosis [81] and myopathies [82].…”

Collisionally activated dissociation of protonated 2′-deoxycytidine, 2′-deoxyuridine, and their oxidatively damaged derivatives

“…odified nucleosides in mammalian cells may arise from posttranscriptional modifications of RNA [1] and oxidative damage of nucleic acids [2,3]. In this respect, more than 100 different types of modified ribonucleosides have been found [1], and many of them play a pivotal role in the structural stability of ribosome and the function of tRNA [4 -6].…”