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RNA Damage (rna + damage)

Distribution by Scientific Domains

Life Sciences	60%

Selected Abstracts

Reactive oxygen species induce RNA damage in human atherosclerosis

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 5 2004
W. Martinet
Abstract Background, Reactive oxygen species (ROS)-induced DNA damage has recently been identified in both human and experimental atherosclerosis. This study was undertaken to investigate whether RNA damage occurs in human atherosclerotic plaques and whether this could be related to oxidative stress. Materials and methods, The integrity of total RNA isolated from carotid endarterectomy specimens (n = 20) and nonatherosclerotic mammary arteries (n = 20) was analyzed using an Agilent 2100 Bioanalyser (Agilent Technologies, Palo Alto, CA). Oxidative modifications of RNA were detected by immunohistochemistry. Results, Eleven out of 20 atherosclerotic plaques showed a significant reduction of the 18S/28S rRNA peaks and a shift in the RNA electropherogram to shorter fragment sizes. In contrast, all mammary arteries showed good-quality RNA with clear 18S and 28S rRNA peaks. Strong nuclear and cytoplasmic immunoreactivity for oxidative damage marker 7,8-dihydro-8-oxo-2,-guanosine (8-oxoG) could be detected in the entire plaque in smooth muscle cells (SMCs), macrophages and endothelial cells, but not in SMCs of adjacent normal media or in mammary arteries. Cytoplasmic 8-oxoG staining in the plaque clearly diminished when tissue sections were pretreated with RNase A, suggesting oxidative base damage of RNA. In vitro treatment of total RNA with ROS-releasing compounds induced RNA degradation. Conclusion, Both loss of RNA integrity and 8-oxoG oxidative modifications were found in human atherosclerotic plaques. Because RNA damage may affect in vitro transcript quantification, RT-PCR results must be interpreted cautiously if independent experimental validation (e.g. evaluation of RNA integrity) is lacking. [source]

RNA damage and surveillance under oxidative stress

IUBMB LIFE, Issue 10 2006
Zhongwei Li
Abstract RNA damage has been recently reported to increase under oxidative stress and in patients with many degenerative diseases, which has drawn attention to the consequences of RNA oxidation at the molecular and cellular levels. Under similar conditions the levels of oxidative damage in RNA are usually higher than those in DNA, which may impair protein synthesis or other RNA function. Therefore, accumulation of RNA damage must be prevented and cells have developed specific mechanisms to remove oxidatively-damaged RNA and to block incorporation of oxidized nucleotides during RNA synthesis. Removal of oxidized RNA may be mediated by specific proteins that recognize oxidative lesions and direct the RNA degradation machinery to eliminate the damaged RNAs. During RNA synthesis, oxidized ribonucleotides are hydrolyzed or discriminated from normal ribonucleotides during transcription, preventing their incorporation into RNA. Collective evidence suggests that RNA oxidative damage is a challenging and persistent problem normally controlled through RNA surveillance mechanisms, making them critical to maintaining cellular health and preventing disease. iubmb Life, 58: 581-588, 2006 [source]

Molecular Beacon Probes of Photodamage in Thymine and Uracil Oligonucleotides,

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2005
Soujanya Yarasi
ABSTRACT Molecular beacons (MB) are becoming more common as sequence-selective detectors of nucleic acids. Although they can easily detect single-base mismatches, they have never been used to directly detect DNA or RNA damage. To measure the degree of ultraviolet (UV) light damage in oligonucleotides, we report a novel MB approach for general detection of photoproducts in UV-irradiated rU17 and dT17 oligonucleotides. With monochromatic UV light irradiation at ca 280 nm under anoxic conditions, the oligonucleotide absorption decays with a single-exponential time constant of 123 ± 1 min for rU17 and with double-exponential time constants of 78 ± 0.5 min (99%) and 180 ± 5 min (0.05%) for dT17 oligonucleotides. Under the same conditions, the MB fluorescence decays more quickly, with single-exponential time constants of 19 ± 2 and 26 ± 3 min for rU17 and dT17, respectively. Similar kinetics were observed with broadband UV light irradiation of oligonucleotides. The differences in the UV damage kinetics of dT17 and rU17 and their detection by absorption and fluorescence techniques will be discussed in the context of differential instabilities introduced in the nucleic acid-MB duplex by the different photoproducts formed. [source]