Graduate School of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama, 236-0027, Japan.
Graduate School of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama, 236-0027, Japan; Ichiban Life Corporation, 1-1-7 Horai-cho, Naka-ku, Yokohama, 231-0048, Japan.
Mech Ageing Dev. 2019 Mar;178:25-32. doi: 10.1016/j.mad.2019.01.001. Epub 2019 Jan 4.
Cellular senescence is a phenomenon of irreversible growth arrest in mammalian somatic cells in culture. Various stresses induce cellular senescence and indeed, we have found that excess thymidine effectively induces cellular senescence in human cells. Further, many reports indicate the implication of chromatin proteins in cellular senescence. Here we analysed the role of lamin B receptor (LBR), a nuclear envelope protein that regulates heterochromatin organization, in cellular senescence induced by excess thymidine. We then found that the LBR protein was down-regulated and showed aberrant localization in cells upon induction of cellular senescence by excess thymidine. Additionally, we also found that knock-down of LBR facilitated the induction of cellular senescence by excess thymidine in cancerous HeLa cells, and importantly, it induced cellular senescence in normal human diploid fibroblast TIG-7 cells. These results suggested that decreased LBR function is involved in the induction of cellular senescence in human cells.
细胞衰老是哺乳动物体细胞在培养中不可逆生长停滞的现象。各种应激诱导细胞衰老，事实上，我们已经发现过量胸苷能有效地诱导人细胞的细胞衰老。此外，许多报道表明染色质蛋白与细胞衰老有关。在这里，我们分析了核膜蛋白 lamin B 受体（LBR）在过量胸苷诱导的细胞衰老中的作用，LBR 调节异染色质的组织。我们发现，在过量胸苷诱导的细胞衰老时，LBR 蛋白下调，并在细胞中出现异常定位。此外，我们还发现，在 HeLa 癌细胞中敲低 LBR 有助于过量胸苷诱导的细胞衰老，重要的是，它还能诱导正常人二倍体成纤维细胞 TIG-7 细胞的细胞衰老。这些结果表明，LBR 功能的降低参与了人细胞的细胞衰老诱导。
