Houben Joyce M J, Moonen Harald J J, van Schooten Frederik J, Hageman Geja J
Department of Health Risk Analysis and Toxicology, Maastricht University, The Netherlands.
Free Radic Biol Med. 2008 Feb 1;44(3):235-46. doi: 10.1016/j.freeradbiomed.2007.10.001. Epub 2007 Oct 10.
Telomeres are nucleoprotein structures, located at the ends of chromosomes and are subject to shortening at each cycle of cell division. They prevent chromosomal ends from being recognized as double strand breaks and protect them from end to end fusion and degradation. Telomeres consist of stretches of repetitive DNA with a high G-C content and are reported to be highly sensitive to damage induced by oxidative stress. The resulting DNA strand breaks can be formed either directly or as an intermediate step during the repair of oxidative bases. In contrast to the majority of genomic DNA, there is evidence that telomeric DNA is deficient in the repair of single strand breaks. Since chronic oxidative stress plays a major role in the pathophysiology of several chronic inflammatory diseases, it is hypothesized that telomere length is reducing at a faster rate during oxidative stress. Therefore, assessment of telomere length might be a useful biomarker of disease progression. In this review several features of telomere length regulation, their relation with oxidative stress, and the potential application of measurement of telomere length as biomarker of chronic oxidative stress, will be discussed.
端粒是位于染色体末端的核蛋白结构，在细胞分裂的每个周期都会缩短。它们可防止染色体末端被识别为双链断裂，并保护其免于端对端融合和降解。端粒由富含鸟嘌呤-胞嘧啶（G-C）的重复DNA序列组成，据报道对氧化应激诱导的损伤高度敏感。由此产生的DNA链断裂可以直接形成，也可以在氧化碱基修复过程中作为中间步骤形成。与大多数基因组DNA不同，有证据表明端粒DNA在单链断裂修复方面存在缺陷。由于慢性氧化应激在几种慢性炎症性疾病的病理生理学中起主要作用，因此推测在氧化应激期间端粒长度以更快的速度缩短。因此，端粒长度评估可能是疾病进展的有用生物标志物。在这篇综述中，将讨论端粒长度调控的几个特征、它们与氧化应激的关系，以及将端粒长度测量作为慢性氧化应激生物标志物的潜在应用。
