关于沃纳综合征和正常成纤维细胞复制性衰老的分子遗传学基础的研究。

Studies on the molecular-genetic basis of replicative senescence in Werner syndrome and normal fibroblasts.

作者信息

Goldstein S, Murano S, Benes H, Moerman E J, Jones R A, Thweatt R, Shmookler Reis R J, Howard B H

机构信息

Department of Medicine, University of Arkansas for Medical Sciences, Little Rock.

出版信息

Exp Gerontol. 1989;24(5-6):461-8. doi: 10.1016/0531-5565(89)90052-1.

DOI:10.1016/0531-5565(89)90052-1

PMID:2632280

Abstract

Based on evidence that human diploid fibroblasts (HDF) from the Werner syndrome (WS) of premature aging might overexpress an inhibitor of DNA synthesis (IDS), we prepared a eukaryotic cDNA expression library from WS mRNA and tested it for IDS activity in a transient assay. Two of six WS cDNA pools tested gave IDS activity, then on plus/minus screening revealed several differentially expressed cDNA clones. By slot blot and Northern analysis, one cDNA clone was found to be overexpressed in WS and normal senescent HDF, but not in quiescent normal HDF, indicating that it is senescence-specific. Further studies are needed to clarify: a) whether this cDNA truly acts as an IDS; b) if so, whether it acts alone or in concert with other cDNAs; and c) whether it is involved in the degenerative and malignant sequelae of WS and normal aging.

摘要

基于有证据表明，来自早衰的沃纳综合征（WS）的人类二倍体成纤维细胞（HDF）可能过度表达一种DNA合成抑制剂（IDS），我们从WS mRNA制备了一个真核cDNA表达文库，并在瞬时分析中测试其IDS活性。所测试的六个WS cDNA文库中有两个具有IDS活性，然后通过正负筛选揭示了几个差异表达的cDNA克隆。通过狭缝印迹和Northern分析，发现一个cDNA克隆在WS和正常衰老的HDF中过度表达，但在静止的正常HDF中不表达，表明它是衰老特异性的。需要进一步研究以阐明：a）该cDNA是否真的作为IDS起作用；b）如果是这样，它是单独起作用还是与其他cDNA协同作用；c）它是否参与WS和正常衰老的退行性和恶性后遗症。