BJ fibroblasts display high antioxidant capacity and slow telomere shortening independent of hTERT transfection

被引:61
作者
Lorenz, M
Saretzki, G
Sitte, N
Metzkow, S
von Zglinicki, T
机构
[1] Newcastle Gen Hosp, Wolfson Res Ctr, Dept Gerontol, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England
[2] Humboldt Univ, Charite, Inst Pathol, Berlin, Germany
[3] Free Univ Berlin, Univ Clin Benjamin Franklin, Berlin, Germany
关键词
fibroblasts; hyperoxia; telomeres; telomerase; senescence; immortality; free radicals;
D O I
10.1016/S0891-5849(01)00664-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human foreskin BJ fibroblasts are well protected against oxidative stress as shown by their low intracellular peroxide content, low levels of protein carbonyls, and low steady-state lipofuscin content as compared to other primary human fibroblasts. This correlates with a long replicative life span of the parental cells of about 90 population doublings and a telomere-shortening rate of only 15-20 bp/PD. This value might define the upper limit of a telomere-shortening rate that can still be explained by the end replication problem alone. In BJ clones immortalized by transfection with hTERT, the catalytic subunit of telomerase, the same telomere-shortening rate as in parental cells is observed over a long time despite strong telomerase activity. Hyperoxia, which induces oxidative stress and accelerates telomere shortening in a variety of human fibroblast strains, does not do so in BJ cells. It is possible that the high antioxidative capacity of BJ cells, by minimizing the accumulation of genomic damage, is instrumental in the successful immortalization of these cells by telomerase. (C) 2001 Elsevier Science Inc.
引用
收藏
页码:824 / 831
页数:8
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