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超氧化物和 DNA 修复对蜥蜴端粒的长期影响。

Long-term effects of superoxide and DNA repair on lizard telomeres.

机构信息

Department of Biological and Environmental Sciences, University of Gothenburg, Gothenburg, Sweden.

School of Biological Sciences, The University of Wollongong, Wollongong, New South Wales, Australia.

出版信息

Mol Ecol. 2018 Dec;27(24):5154-5164. doi: 10.1111/mec.14913. Epub 2018 Dec 10.

DOI:10.1111/mec.14913
PMID:30368957
Abstract

Telomeres are the non-coding protein-nucleotide "caps" at chromosome ends that contribute to chromosomal stability by protecting the coding parts of the linear DNA from shortening at cell division, and from erosion by reactive molecules. Recently, there has been some controversy between molecular and cell biologists, on the one hand, and evolutionary ecologists on the other, regarding whether reactive molecules erode telomeres during oxidative stress. Many studies of biochemistry and medicine have verified these relationships in cell culture, but other researchers have failed to find such effects in free-living vertebrates. Here, we use a novel approach to measure free radicals (superoxide), mitochondrial "content" (a combined measure of mitochondrial number and size in cells), telomere length and DNA damage at two primary time points during the mating season of an annual lizard species (Ctenophorus pictus). Superoxide levels early in the mating season vary widely and elevated levels predict shorter telomeres both at that time as well as several months later. These effects are likely driven by mitochondrial content, which significantly impacts late season superoxide (cells with more mitochondria have more superoxide), but superoxide effects on telomeres are counteracted by DNA repair as revealed by 8-hydroxy-2'-deoxyguanosine assays. We conclude that reactive oxygen species and DNA repair are fundamental for both short- and long-term regulation of lizard telomere length with pronounced effects of early season cellular stress detectable on telomere length near lizard death.

摘要

端粒是染色体末端的非编码蛋白-核苷酸“帽”,通过保护线性 DNA 的编码部分在细胞分裂时不会缩短,以及防止被反应性分子侵蚀,从而有助于染色体稳定。最近,分子和细胞生物学家与进化生态学家之间存在一些争议,即反应性分子是否在氧化应激期间侵蚀端粒。许多生物化学和医学研究已经在细胞培养中验证了这些关系,但其他研究人员在自由生活的脊椎动物中没有发现这种影响。在这里,我们使用一种新方法来测量自由基(超氧化物)、线粒体“含量”(细胞中线粒体数量和大小的综合衡量标准)、端粒长度和 DNA 损伤,这两个指标是在年度蜥蜴物种(Ctenophorus pictus)的交配季节的两个主要时间点进行测量的。交配季节早期的超氧化物水平变化很大,高水平预示着此时以及几个月后端粒较短。这些影响可能是由线粒体含量驱动的,线粒体含量显著影响后期的超氧化物(线粒体越多的细胞产生的超氧化物越多),但 DNA 修复会抵消超氧化物对端粒的影响,这可以通过 8-羟基-2'-脱氧鸟苷检测来揭示。我们的结论是,活性氧和 DNA 修复对于蜥蜴端粒长度的短期和长期调节都是基本的,早期细胞应激对端粒长度的明显影响可检测到蜥蜴死亡附近的端粒长度。

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