Human polynucleotide phosphorylase protein in response to oxidative stress
Human polynucleotide phosphorylase protein in response to oxidative stress
复制标题
DOI：
10.1021/bi052585l
复制
发表时间：
2006-05-30
期刊：
影响因子：
2.9
通讯作者：
Sekiguchi, Mutsuo
中科院分区：
文献类型：
--
作者：
Hayakawa, Hiroshi;Sekiguchi, Mutsuo
8-氧代-7，8-二氢鸟嘌呤（8-oxoGua）是在核酸及其前体中产生的，这是由于通过正常细胞代谢产生的氧自由基的作用。由于氧化鸟嘌呤可以与胞嘧啶和腺嘌呤配对，当它存在于RNA中时，它会导致表型表达的改变。为了防止这种结果，生物体必须有某种机制来消除RNA及其前体中的氧化鸟嘌呤核苷酸。在哺乳动物细胞中，MTH 1和NUDT 5蛋白将8-oxoGTP和8-oxoGDP降解为8-oxoGMP，这是一种无法用于RNA合成的形式。在寻找在RNA水平发挥作用的蛋白质中，多核苷酸磷酸化酶（PNP）蛋白被认为是这种作用的良好候选者。人PNP蛋白具有特异性结合含有8-oxoGua的RNA的能力。当人类细胞暴露于诱导氧化应激的试剂，如过氧化氢和甲萘醌时，PNP蛋白质的量迅速减少，而细胞中其他蛋白质的量在这样的处理后不改变。当用足以提供相同程度的生长抑制的剂量的ACNU和放线菌酮处理细胞时，未观察到PNP蛋白水平的特异性降低。这些结果意味着PNP蛋白可能因此在将氧化形式的RNA排除在翻译机制之外方面发挥作用。
8-Oxo-7,8-dihydroguanine (8-oxoGua) is generated in nucleic acids as well as in their precursors due to the actions of oxygen radicals produced through a normal cellular metabolism. Since oxidized guanine can pair with both cytosine and adenine, it causes alterations in the phenotypic expression when it is present in RNA. To prevent such an outcome, organisms must have some mechanism for eliminating such oxidized guanine nucleotides from RNA and its precursors. In mammalian cells, MTH1 and NUDT5 proteins degrade 8-oxoGTP and 8-oxoGDP to 8-oxoGMP, which is an unusable form for RNA synthesis. In a search for proteins functioning at the RNA level, polynucleotide phosphorylase (PNP) protein has been suggested to be a good candidate for such a role. The human PNP protein has an ability to bind specifically to RNA containing 8-oxoGua. When human cells are exposed to agents that induce oxidative stress, such as hydrogen peroxide and menadion, the amounts of PNP protein decrease rapidly while amounts of other proteins in the cells do not change after such treatments. No specific decrease in the PNP protein level is observed when cells are treated with ACNU and cycloheximide at doses sufficient to provide the same degree of growth suppression. These results imply that the PNP protein might thus play a role in excluding oxidized forms of RNA from the translation mechanism.