Human polynucleotide phosphorylase reduces oxidative RNA damage and protects HeLa cell against oxidative stress.
Human polynucleotide phosphorylase reduces oxidative RNA damage and protects HeLa cell against oxidative stress.
复制标题
DOI：
10.1016/j.bbrc.2008.05.058
复制
发表时间：
2008-07
影响因子：
3.1
通讯作者：
Jinhua Wu;Zhongwei Li
中科院分区：
文献类型：
--
作者：
Jinhua Wu;Zhongwei Li
我们研究了HeLa细胞的活力和RNA氧化损伤响应过氧化氢（H2 O2）处理。受损RNA的水平，通过8-羟基鸟苷（7，8-dihydro-8-oxoguanosine，8-oxoG）的含量来测量，取决于H2 O2剂量而增加，并且与细胞活力呈负相关。在去除氧化攻击后，RNA中升高的8-oxoG水平降低，表明存在用于清除氧化RNA的监视机制。人多核苷酸磷酸化酶（hPNIPs）是一种主要位于线粒体中的核糖核酸外切酶，先前已显示以高亲和力结合8-oxoG-RNA。在此研究了hPNTR在氧化应激条件下HeLa细胞中的作用。过表达hPNTR可减少RNA氧化，提高细胞对H2 O2损伤的存活率。相反，hPNO 3敲低降低了生存力，并增加了8-oxoG水平在HeLa细胞暴露于H2 O2。我们的研究结果表明，hPNIPs在氧化应激下保护细胞和限制受损的RNA中起着重要作用。
We examined HeLa cell viability and RNA oxidative damage in response to hydrogen peroxide (H2O2) treatment. The level of damaged RNA, measured by the content of 8-hydroxyguanosine (7,8-dihydro-8-oxoguanosine, 8-oxoG), increases depending on H2O2dosage and is inversely correlated with cell viability. The elevated level of 8-oxoG in RNA decreases after removal of oxidative challenge, suggesting the existence of surveillance mechanism(s) for cleaning up oxidized RNA. Human polynucleotide phosphorylase (hPNPase), an exoribonuclease primarily located in mitochondria, has been previously shown to bind 8-oxoG-RNA with high affinity. The role of hPNPase in HeLa cell under oxidative stress conditions is examined here. Overexpression of hPNPase reduces RNA oxidation and increases cell viability against H2O2insult. Conversely, hPNPase knockdown decreases viability and increases 8-oxoG level in HeLa cell exposed to H2O2. Our results suggest that hPNPase plays an important role in protecting cells and limiting damaged RNA under oxidative stress.