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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。

相似文献

1
Studies on the molecular-genetic basis of replicative senescence in Werner syndrome and normal fibroblasts.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。
Exp Gerontol. 1989;24(5-6):461-8. doi: 10.1016/0531-5565(89)90052-1.
2
Diverse gene sequences are overexpressed in werner syndrome fibroblasts undergoing premature replicative senescence.在经历过早复制性衰老的沃纳综合征成纤维细胞中,多种基因序列过度表达。
Mol Cell Biol. 1991 Aug;11(8):3905-14. doi: 10.1128/mcb.11.8.3905-3914.1991.
3
Werner syndrome and biological ageing: a molecular genetic hypothesis.
Bioessays. 1993 Jun;15(6):421-6. doi: 10.1002/bies.950150609.
4
Identification of gene sequences overexpressed in senescent and Werner syndrome human fibroblasts.在衰老和沃纳综合征人类成纤维细胞中过表达的基因序列的鉴定。
Exp Gerontol. 1996 Jan-Apr;31(1-2):159-74. doi: 10.1016/0531-5565(95)02014-4.
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Altered regulation of fibronectin gene expression in Werner syndrome fibroblasts.沃纳综合征成纤维细胞中纤连蛋白基因表达的调控改变。
Exp Cell Res. 1994 Jul;213(1):121-7. doi: 10.1006/excr.1994.1181.
6
Analysis of the primary structure of insulin-like growth factor binding protein-3 cDNA from Werner syndrome fibroblasts.沃纳综合征成纤维细胞中胰岛素样生长因子结合蛋白-3 cDNA的一级结构分析。
DNA Seq. 1993;4(1):43-6. doi: 10.3109/10425179309015621.
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Regulation of c-fos expression in senescing Werner syndrome fibroblasts differs from that observed in senescing fibroblasts from normal donors.衰老的沃纳综合征成纤维细胞中c-fos表达的调控与正常供体衰老成纤维细胞中观察到的情况不同。
J Cell Physiol. 1995 Feb;162(2):277-83. doi: 10.1002/jcp.1041620213.
8
Investigation of the signaling pathways involved in the proliferative life span barriers in werner syndrome fibroblasts.对沃纳综合征成纤维细胞增殖寿命障碍中涉及的信号通路的研究。
Ann N Y Acad Sci. 2004 Jun;1019:274-7. doi: 10.1196/annals.1297.046.
9
Homologous recombination is elevated in some Werner-like syndromes but not during normal in vitro or in vivo senescence of mammalian cells.同源重组在某些沃纳样综合征中会增加,但在哺乳动物细胞正常的体外或体内衰老过程中不会增加。
Mutat Res. 1990 Sep-Nov;237(5-6):259-69. doi: 10.1016/0921-8734(90)90008-f.
10
No increase in senescence-associated beta-galactosidase activity in Werner syndrome fibroblasts after exposure to H2O2.暴露于过氧化氢后,沃纳综合征成纤维细胞中衰老相关β-半乳糖苷酶活性未增加。
Ann N Y Acad Sci. 2004 Jun;1019:375-8. doi: 10.1196/annals.1297.066.

引用本文的文献

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Regulation of senescence in cancer and aging.癌症与衰老过程中衰老的调控。
J Aging Res. 2011 Mar 8;2011:963172. doi: 10.4061/2011/963172.
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Cell cycle arrest by human cytomegalovirus 86-kDa IE2 protein resembles premature senescence.人巨细胞病毒86-kDa IE2蛋白导致的细胞周期停滞类似于早衰。
J Virol. 2002 Dec;76(23):12135-48. doi: 10.1128/jvi.76.23.12135-12148.2002.
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An overexpressed gene transcript in senescent and quiescent human fibroblasts encoding a novel protein in the epidermal growth factor-like repeat family stimulates DNA synthesis.
在衰老和静止的人成纤维细胞中过度表达的一种基因转录本,编码表皮生长因子样重复序列家族中的一种新型蛋白质,可刺激DNA合成。
Mol Cell Biol. 1995 Jan;15(1):120-8. doi: 10.1128/MCB.15.1.120.
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A case of Werner's syndrome associated with systemic lupus erythematosus.一例与系统性红斑狼疮相关的沃纳综合征病例。
Clin Rheumatol. 1995 Mar;14(2):199-203. doi: 10.1007/BF02214944.
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Insulin-like growth factor binding protein 3 accumulates to high levels in culture medium of senescent and quiescent human fibroblasts.胰岛素样生长因子结合蛋白3在衰老和静止的人成纤维细胞培养基中积累至高水平。
Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9680-4. doi: 10.1073/pnas.88.21.9680.
6
Diverse gene sequences are overexpressed in werner syndrome fibroblasts undergoing premature replicative senescence.在经历过早复制性衰老的沃纳综合征成纤维细胞中,多种基因序列过度表达。
Mol Cell Biol. 1991 Aug;11(8):3905-14. doi: 10.1128/mcb.11.8.3905-3914.1991.