期刊
ARCHIVES OF MEDICAL RESEARCH
卷 43, 期 1, 页码 15-20出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.arcmed.2012.02.001
关键词
Hypoxia; Telomere; Subtelomere; DNA methylation; Telomerase; Endothelial cell
资金
- NSFC [81170329/H2501]
- Ministry of Education, Science, and Culture of Japan [23590885]
- Grants-in-Aid for Scientific Research [23590885] Funding Source: KAKEN
Background and Aims. Hypoxia-associated changes of telomeric structure in cell cultures have been analyzed mainly in cancer cells, stem cells, or cells transduced with vectors containing the telomerase gene, but not in somatic cells. The stability of telomere structure has been reported to be associated with subtelomeric methylation status. However, there are no reports of epigenetic alterations of telomeric regions of human somatic cells under hypoxia. This study aims at detecting and analyzing the subtelomeric methylation status in human somatic cells cultured under hypoxia. Methods. Mean telomere length and telomerase activity of human umbilical vein endothelial cells (HUVECs) cultured in hypoxic conditions were measured. Subtelomeric methylation status of these cells was assessed by genomic Southern blot with telomere DNA probe using methylation-sensitive and -insensitive isoschizomers, MspI and HpaII. Results. The telomerase activity in HUVECs correlated inversely with the oxygen concentration. Mild hypoxia (10 or 15% oxygen) increased the telomere lengths, whereas the telomere lengths did not appear to change when <1% O-2. The subtelomere of the shortest telomere range was methylated the most at 1% O-2. Conclusions. Subtelomeric hypermethylation of short telomeres at 1% O-2 compared to milder hypoxia implied that the subtelomeric hypermethylation may yield telomere stability and favor the cell survival of short telomere-bearing cells. (C) 2012 IMSS. Published by Elsevier Inc.
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