The effects of oxidative stress on telomerase activity and other stress-related proteins in lens epithelial cells
The effects of oxidative stress on telomerase activity and other stress-related proteins in lens epithelial cells
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DOI：
10.1016/j.exer.2003.10.019
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发表时间：
2004-02-01
影响因子：
3.4
通讯作者：
Warren, J
中科院分区：
文献类型：
--
作者：
Colitz, CMH;Whittington, A;Warren, J
端粒酶是一种核糖核蛋白复合物，负责维持染色体末端和修复DNA链断裂。端粒酶活性通常存在于具有无限增殖潜力的细胞中，如肿瘤细胞、生殖细胞和一些干细胞，而晶状体上皮细胞（虽然不是高度增殖的）也有端粒酶活性。我们之前的研究表明，尽管晶状体上皮细胞的增殖潜力较低，但端粒酶的表达水平很高，因此我们假设端粒酶的表达可以保护晶状体上皮细胞免受氧化应激的影响。我们还测定了应激蛋白gadd45和p16以及应激和增殖相关蛋白增殖细胞核抗原（PCNA）的水平。在急性研究中，晶状体暴露于TBHP 0-120分钟。在恢复研究中，镜片暴露在TBHP下1小时，然后允许恢复18小时。在急性研究中，端粒酶活性升高，p16先降低后正常化，PCNA水平即使在夜间恢复组也没有明显变化，gadd45在一些暴露组中降低。在恢复研究中，各组端粒酶活性均升高，gadd45先降低后升高，p16水平在恢复后期降低。在研究期间，PCNA水平保持不变，表明增殖没有变化。这些研究表明端粒酶活性升高与晶状体上皮细胞增殖增加无关；相反，端粒酶活性的增加与压力相关蛋白gadd45水平的增加只有在恢复后期才有关联。这些发现支持了端粒酶在晶状体上皮细胞中起保护作用而不是增殖作用的假设。(C) 2003 Elsevier Ltd.版权所有。
Telomerase is a ribonucleoprotein complex responsible for maintaining the ends of chromosomes and for repair of DNA strand breaks. While telomerase activity is generally found in cells that have unlimited proliferative potential such as neoplastic cells, germline cells and some stem cells, lens epithelial cells (though not highly proliferative) have telomerase activity. Our previous studies indicated that lens epithelial cells express high levels of telomerase despite their low proliferative potential, thus we hypothesized that telomerase expression protects lens epithelial cells from oxidative stress. We also determined levels of the stress proteins gadd45 and p16 and the stress and proliferation-related protein, proliferating cell nuclear antigen (PCNA). In acute studies, lenses were exposed to TBHP for 0-120 min. In recovery studies, lenses were exposed to TBHP for 1 hr, then allowed to recover for up to 18 hr. In acute studies, telomerase activity was increased, p16 initially decreased then normalized, PCNA levels did not change significantly even in the overnight recovery groups, and gadd45 was decreased in some TBHP exposed groups. In recovery studies, telomerase activity was increased in all groups, gadd45 decreased then became elevated, and p16 levels were decreased at later recovery times. PCNA levels remained constant during the studies, indicating that there was no change in proliferation. These studies showed that elevated telomerase activity did not correlate with increased proliferation in lens epithelial cells; instead, increased telomerase activity was associated with increased levels of the stress-related protein gadd45 only in the later recovery times. These findings support the hypothesis that telomerase plays a protective rather than a proliferative role in lens epithelial cells. (C) 2003 Elsevier Ltd. All rights reserved.