Dick J E, Wright J A
Mech Ageing Dev. 1985 Oct 14;32(1):85-97. doi: 10.1016/0047-6374(85)90038-7.
Changes in ribonucleotide reductase occur during the senescence of normal human diploid fibroblasts in culture. Enzyme activity is significantly lower in cells and extracts at high mean population doublings (MPD) as compared to fibroblasts at low MPD. Although many of the kinetic properties of the enzyme remain unaltered in cells at high MPD, changes in the extent and kinetic mechanism of inhibition of CDP and ADP reductase activity by dATP, the overall negative effector of ribonucleotide reductase, were observed. These results and a previous observation that the four deoxyribonucleotide pools are markedly altered during in vitro senescence of human diploid fibroblasts, provide evidence for a link between ribonucleotide reduction, deoxyribonucleotide pools, and the establishment of the non-proliferative or senescent state.
在培养的正常人二倍体成纤维细胞衰老过程中，核糖核苷酸还原酶会发生变化。与低平均群体倍增数（MPD）的成纤维细胞相比，高MPD的细胞和提取物中的酶活性显著降低。尽管该酶的许多动力学特性在高MPD的细胞中保持不变，但观察到核糖核苷酸还原酶的总体负效应物dATP对CDP和ADP还原酶活性的抑制程度和动力学机制发生了变化。这些结果以及先前的一项观察结果，即人类二倍体成纤维细胞在体外衰老过程中四个脱氧核糖核苷酸池会发生显著改变，为核糖核苷酸还原、脱氧核糖核苷酸池与非增殖或衰老状态的建立之间的联系提供了证据。
