Elevation in the ratio of Cu/Zn-superoxide dismutase to glutathione peroxidase activity induces features of cellular senescence and this effect is mediated by hydrogen peroxide
Elevation in the ratio of Cu/Zn-superoxide dismutase to glutathione peroxidase activity induces features of cellular senescence and this effect is mediated by hydrogen peroxide
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DOI：
10.1093/hmg/5.2.283
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发表时间：
1996-02-01
影响因子：
3.5
通讯作者：
Kola, I
中科院分区：
文献类型：
--
作者：
deHaan, JB;Cristiano, F;Kola, I
尽管活性氧物质被认为在衰老过程中起主要作用，但确切的分子机制仍不清楚。在这项研究中，我们研究了铜/锌超氧化物歧化酶活性（Sod1将超氧阴离子 -O - 2(-)歧化为H₂O₂）与谷胱甘肽过氧化物酶活性（Gpx1催化H₂O₂转化为H₂O）的比值变化对细胞生长和发育的影响。我们的数据表明，Sod1转染的细胞系中，Sod1活性与Gpx1活性的比值升高会产生更高水平的H₂O₂，并表现出细胞衰老的典型特征，即增殖减缓且形态改变。相反，Sod1转染的细胞系中这两种酶的活性比值未改变，H₂O₂水平也未改变，且未表现出衰老特征。此外，与相应的对照组相比，从唐氏综合征患者建立的成纤维细胞中Sod1与Gpx1活性的比值增加，且更早衰老。有趣的是，用H₂O₂处理的细胞也表现出衰老特征和/或更早衰老。我们还表明，在唐氏综合征细胞、Sod1与Gpx1活性比值改变的Sod1转染细胞以及用H₂O₂处理的细胞中，Cip1 mRNA水平升高，这表明增殖缓慢可能是由Cip1介导的。此外，我们的数据表明，细胞暴露于H₂O₂会诱导Cip1 mRNA水平升高。这些数据为有助于细胞衰老的可能分子机制提供了有价值的见解，并可能有助于衰老治疗策略的发展。
Although reactive oxygen species have been proposed to play a major role in the aging process, the exact molecular mechanisms remain elusive, In this study we investigate the effects of a perturbation in the ratio of Cu/Zn-superoxide dismutase activity (Sod1 dismutases -O-2(-) to H2O2) to glutathione peroxidase activity (Gpx1 catalyses H2O2 conversion to H2O) on cell growth and development, Our data demonstrate that Sod1 transfected cell lines that have an elevation in the ratio of Sod1 activity to Gpxl activity produce higher levels of H2O2 and exhibit well characterised markers of cellular senescence viz.slower proliferation and altered morphology, On the contrary, Sod1 transfected cell lines that have an unaltered ratio in the activity of these two enzymes, have unaltered levels of H2O2 and fail to show characteristics of senescence, Furthermore, fibroblasts established from individuals with Down syndrome have an increase in the ratio of Sod1 to Gpx1 activity compared with corresponding controls and senesce earlier, Interestingly, cells treated with H2O2 also show features of senescence and/or senesce earlier, We also show that Cip1 mRNA levels are elevated in Down syndrome cells, Sod1 transfectants with an altered Sod1 to Gpxl activity ratio and those treated with H2O2 thus suggesting that the slow proliferation may be mediated by Cip1. Furthermore, our data demonstrate that Cip1 mRNA levels are induced by exposure of cells to H2O2 These data give valuable insight into possible molecular mechanisms that contribute to cellular senescence and may be useful in the evolution of therapeutic strategies for aging.