Age-dependent down-regulation of DNA polymerase δ1 in human lymphocytes
Age-dependent down-regulation of DNA polymerase δ1 in human lymphocytes
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DOI：
10.1007/s11010-012-1432-6
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发表时间：
2012-12-01
影响因子：
4.3
通讯作者：
Liu, Chen-Geng
中科院分区：
文献类型：
--
作者：
Wang, Jin-Ling;Guo, Hong-Lin;Liu, Chen-Geng
衰老进程和功能活动的退化主要归因于DNA修复潜能的降低。DNA聚合酶(DNA polymerase, pol) δ酶活性在基因组稳定性中起着至关重要的作用，因为它具有重要的DNA复制和修复能力。为了阐明DNA pol delta在衰老过程中的作用，我们首先检测了其催化亚基DNA pol delta 1在不同年龄阶段的人淋巴细胞中的表达，然后在体内观察疾病对DNA pol delta 1的影响，在体外观察营养对2BS细胞中DNA pol delta 1表达的影响。分别采集健康人、糖尿病和冠心病患者的血样，采用RT-PCR和western blot方法分析DNA pol delta 1的转录和蛋白表达。将2BS细胞PD30和PD47分别培养于正常培养基和其他不同营养的培养基中，验证DNA pol delta 1的差异表达。结果表明，随着年龄的增长，DNA pol δ 1 mRNA的表达量显著下降，蛋白质水平与基因水平基本一致。此外，DNA pol δ 1的表达在健康个体和年龄匹配的患者组之间没有显著差异。此外，DNA pol δ 1基因的表达水平不受营养状况的影响。我们的研究结果共同证实了DNA pol δ 1的下调与年龄有关，与疾病和营养几乎没有关系。DNA pol δ 1作为一种新的衰老生物标志物具有很大的潜力。
Aging progress and degeneracy of functional activity are mainly attributed to the decreased DNA repair potential. DNA polymerase (pol) delta activity plays an essential role in genome stability by virtue of its crucial DNA replication and repair capacity. To order to clarify the role of DNA pol delta in aging progression, we firstly examined the expressions of its catalytic subunit named DNA pol delta 1 in human lymphocytes at different age stages, respectively, and then observed the effect of diseases on DNA pol delta 1 in vivo and of nutriture on its expressions in 2BS cells in vitro. Blood samples from the healthy subjects and patients with diabetes mellitus and coronary heart disease were collected, respectively, for analysis of transcription and protein expressions of DNA pol delta 1 by RT-PCR and western blot. 2BS cells of PD30 and PD47 were incubated in both normal medium and other mediums of different nutritures for verifying the differential expressions of DNA pol delta 1. Results showed that the mRNA expression of DNA pol delta 1 decreased substantially with age and the protein levels were well consistent with gene levels. Furthermore, there were no significant differences in DNA pol delta 1 expressions between the groups of healthy individuals and the age matched patients. In addition, DNA pol delta 1 gene expression levels were not affected by nutritional status in vitro. Our findings collectively confirmed that the down-regulations of DNA pol delta 1 are age-related and have little bearing on diseases and nutritures. DNA pol delta 1 has great potential for a new biomarker of aging.