Salminen A, Helenius M, Lahtinen T, Korhonen P, Tapiola T, Soininen H, Solovyan V
Department of Neuroscience and Neurology, University of Kuopio, Finland.
Biochem Biophys Res Commun. 1997 Sep 29;238(3):712-6. doi: 10.1006/bbrc.1997.7371.
During aging and cellular senescence mutations accumulate in genomic and mitochondrial DNA. Ku autoantigens, DNA-dependent protein kinase, and poly (ADP-ribose) polymerase have an essential role in DNA damage recognition. Our purpose was to find out whether cellular senescence of fibroblasts affects the protein components that recognize DNA damage and induce the repair process. We compared presenescent and replicatively senescent human WI-38 fibroblasts with each other and with SV-40 immortalized and serum-deficient quiescent WI-38 cells. Our results showed that replicative senescence significantly decreased the nuclear level of both p70 and p86 components of Ku autoantigen. SV-40 immortalization and cellular quiescence did not affect the level of the p86 component but slightly increased that of p70. Both replicative senescence and cellular quiescence decreased the activity of DNA-dependent protein kinase in WI-38 fibroblasts. On the other hand, SV-40 immortalization increased the activity of DNA-dependent protein kinase. The protein level of poly(ADP-ribose) polymerase (PARP) was strongly decreased in replicatively senescent fibroblasts. Quiescence of early-passage fibroblasts also slightly reduced the protein level of PARP. Apoptosis was not observed in replicatively senescent fibroblasts. Our results show that replicative senescence and to some extent cellular quiescence down-regulate the recognition system of DNA damage involving Ku autoantigens, DNA-dependent protein kinase, and PARP and hence could enhance the accumulation of DNA damage during aging.
在衰老和细胞衰老过程中，基因组DNA和线粒体DNA会积累突变。Ku自身抗原、DNA依赖性蛋白激酶和聚（ADP - 核糖）聚合酶在DNA损伤识别中起重要作用。我们的目的是研究成纤维细胞的细胞衰老是否会影响识别DNA损伤并诱导修复过程的蛋白质成分。我们将早老的和复制衰老的人WI - 38成纤维细胞相互比较，并与SV - 40永生化和血清缺乏静止的WI - 38细胞进行比较。我们的结果表明，复制衰老显著降低了Ku自身抗原p70和p86成分的核水平。SV - 40永生化和细胞静止不影响p86成分的水平，但使p70水平略有升高。复制衰老和细胞静止均降低了WI - 38成纤维细胞中DNA依赖性蛋白激酶的活性。另一方面，SV - 40永生化增加了DNA依赖性蛋白激酶的活性。在复制衰老的成纤维细胞中，聚（ADP - 核糖）聚合酶（PARP）的蛋白质水平大幅降低。早期传代成纤维细胞的静止也略微降低了PARP的蛋白质水平。在复制衰老的成纤维细胞中未观察到凋亡。我们的结果表明，复制衰老以及在一定程度上细胞静止会下调涉及Ku自身抗原、DNA依赖性蛋白激酶和PARP的DNA损伤识别系统，因此可能会增强衰老过程中DNA损伤的积累。
