Sitte N, Saretzki G, von Zglinicki T
Institute of Pathology, Charité, Humboldt-University Berlin, Germany.
Free Radic Biol Med. 1998 Apr;24(6):885-93. doi: 10.1016/s0891-5849(97)00363-8.
Telomere length in MRC-5 fibroblasts remains constant if the cells are proliferation-inhibited for up to 3 months by confluency. However, the apparent frequency of single-stranded sites in telomeres, measured as sensitivity to degradation by S1 nuclease, increases about fourfold during this extended inhibition of proliferation. After release of the cells, the frequency of telomeric single-stranded sites decreases to control values, and the telomere shortening rate increases about threefold as compared to controls proliferating without inhibition. This acceleration is transitory, the telomere shortening rate decreases to control values after about two population doublings after release. Finally, temporarily arrested fibroblast populations senesce at a lower cumulative population doubling level, but at about the same telomere length, as continuously proliferating controls. The data suggest that metabolic time-dependent single-strand degradation is a major cause of telomere shortening. They support the idea that telomere shortening plays an important role in triggering cellular senescence.
如果MRC - 5成纤维细胞因汇合而增殖抑制长达3个月，其端粒长度保持恒定。然而，以对S1核酸酶降解的敏感性来衡量，端粒中单链位点的表观频率在这种延长的增殖抑制期间增加约四倍。细胞释放后，端粒单链位点的频率降至对照值，并且与未受抑制增殖的对照相比，端粒缩短率增加约三倍。这种加速是暂时的，释放后约两个群体倍增后端粒缩短率降至对照值。最后，暂时停滞的成纤维细胞群体在较低的累积群体倍增水平下衰老，但端粒长度与持续增殖的对照大致相同。数据表明，代谢时间依赖性单链降解是端粒缩短的主要原因。它们支持端粒缩短在触发细胞衰老中起重要作用的观点。
