TY - JOUR
T1 - Alteration of Telomere Length and Subtelomeric Methylation in Human Endothelial Cell Under Different Levels of Hypoxia
AU - Guan, Jing Zhi
AU - Guan, Wei Ping
AU - Maeda, Toyoki
AU - Makino, Naoki
N1 - Funding Information:
This work was supported, in part, by the National Natural Science Fund (NSFC) ( 81170329/H2501 ) and by a Grant-in-Aid from the Ministry of Education, Science, and Culture of Japan ( #23590885 ).
PY - 2012/1
Y1 - 2012/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.arcmed.2012.02.001
DO - 10.1016/j.arcmed.2012.02.001
M3 - Article
C2 - 22374245
AN - SCOPUS:84859254728
SN - 0188-4409
VL - 43
SP - 15
EP - 20
JO - Archives of Medical Research
JF - Archives of Medical Research
IS - 1
ER -
