Oxidative stress causes a general, calcium-dependent degradation of mitochondrial polynucleotides
Oxidative stress causes a general, calcium-dependent degradation of mitochondrial polynucleotides
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DOI：
10.1016/s0891-5849(98)00143-9
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发表时间：
1998-12-01
影响因子：
7.4
通讯作者：
Davies, KJA
中科院分区：
文献类型：
--
作者：
Crawford, DR;Abramova, NE;Davies, KJA
氧化应激对生物细胞有许多影响，包括对基因表达的调控。已知的是，在原核和真核细胞中，活性氧能上调和下调RNA的表达。我们先前已经报道，当HA-I仓鼠成纤维细胞暴露于过氧化氢时，线粒体RNA发生优先的和钙依赖的下调。在这里，我们扩展这些研究，以确定这种下调是否是线粒体RNA特有的，还是涉及一般的多核苷酸降解。细胞暴露于400 mU M过氧化氢后2小时和5小时16S线粒体rRNA的降解和相应水平的降低与钙有关。线粒体基因组DNA的降解也在过氧化氢暴露后观察到，并且发生在与线粒体RNA降解相似的时间点。与线粒体RNA降解一样，线粒体基因组DNA的这种降解依赖于钙。这些结果表明，在HA-1成纤维细胞暴露于氧化应激后，线粒体多核苷酸普遍存在钙依赖的降解，并表明线粒体生物合成的急剧停止是对氧化应激的早期反应。(C)1998年爱思唯尔科学公司。
Oxidative stress has many effects on biological cells, including the modulation of gene expression. Reactive oxygen species are known to up-regulate and down-regulate RNA expression in prokaryotic and eukaryotic cells. We have previously reported that a preferential and calcium-dependent down-regulation of mitochondrial RNAs occurs when HA-I hamster fibroblasts are exposed to hydrogen peroxide. Here we extend these studies to determine whether this down-regulation is specific to mitochondria RNA or involves general polynucleotide degradation. Degradation and associated decreases in the levels of 16S mitochondrial rRNA following exposure of cells to 400 mu M hydrogen peroxide were found to be dependent on calcium at 2 and 5 h. Degradation of mitochondrial genomic DNA was also observed following peroxide exposure, and occurred at similar time points as for mitochondrial RNA degradation. As with mitochondrial RNA degradation, this mitochondrial genomic DNA degradation was dependent on calcium. These results indicate that-there is a general, calcium-dependent degradation of mitochondrial polynucleotides following exposure of HA-1 fibroblasts to oxidative stress, and suggest that a dramatic shut-down in mitochondrial biosynthesis is an early-stage response to oxidative stress. (C) 1998 Elsevier Science Inc.