The nucleotide pool is a significant target for oxidative stress

被引:117
作者
Haghdoost, Siarnak [1 ]
Sjolander, Lena [1 ]
Czene, Stefan [1 ]
Hanns-Ringdahl, Mats [1 ]
机构
[1] Stockholm Univ, Dept Genet Microbiol & Toxicol, S-10691 Stockholm, Sweden
关键词
8-oxo-dG; S-OH-dG; nucleotide pool; hMTH1; siRNA; radiation; oxidative stress; free radicals;
D O I
10.1016/j.freeradbiomed.2006.05.003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Oxidative stress is considered to be one of the most important phenomena involved in the process of aging and age-related diseases. 8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) has been frequently used as a marker for oxidative stress. However, the origin of extracellular 8-oxo-dG is not well understood. The aim of this work was to investigate the nucleotide pool and the role of the human muff homologue protein (hMTH1) in the appearance of extracellular 8-oxo-dG in a cellular model system. For this purpose we used primary human fibroblast cells, which were transfected by siRNAs homologous to hMTH1. Extracellular 8-oxo-dG in cell culture media after exposure of the cells to ionizing radiation was measured as enzyme-linked immunosorbent assay reactivity. Our results demonstrate the profound effect of both hMTH1 expression and nucleotide pool size on the cellular excretion of 8-oxo-dG, suggesting that the nucleotide pool is a significant target for the formation of extracellular 8-oxo-dG. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:620 / 626
页数:7
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