Telomerase protects developing neurons against DNA damage-induced cell death

被引:59
作者
Lu, CB
Fu, WM
Mattson, MP
机构
[1] NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA
[2] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA
来源
DEVELOPMENTAL BRAIN RESEARCH | 2001年 / 131卷 / 1-2期
关键词
apoptosis; camptothecin; cancer; etoposide; hippocampus; p53; TERT; topoisomerase;
D O I
10.1016/S0165-3806(01)00237-1
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
In mitotic cells, telomerase adds repeats of a DNA sequence (TTAGGG) to the ends of chromosomes (telomeres) thereby maintaining their length and preventing cellular senescence. We recently reported that the catalytic subunit of telomerase (TERT) is expressed in neuronal progenitor cells and in early postmitotic neurons in the developing rodent brain. We now report that TERT can protect cultured PC12 cells and embryonic hippocampal neurons against death induced by DNA damage. Overexpression of TERT in PC12 cells increases their resistance to the topoisomerase inhibitors camptothecin and etoposide. Hippocampal neurons in which TERT levels are decreased using antisense technology exhibit increased vulnerability to the DNA-damaging agents. Emerging findings suggest that DNA damage may trigger the death of neurons during brain development and in neurodegenerative disorders. Our data therefore suggest roles for TERT in modulating such cell deaths. Published by Elsevier Science B.V.
引用
收藏
页码:167 / 171
页数:5
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