Skip to main content
SpringerLink
Log in

Changes in telomere length distribution in low-dose X-ray-irradiated human umbilical vein endothelial cells

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Ionizing radiation (IR) is known to be a cause of telomere dysfunction in tumor cells; however, very few studies have investigated X-ray-related changes in telomere length and the telomerase activity in normal human cells, such as umbilical vein endothelial cells (HUVECs). The loss of a few hundred base pairs from a shortened telomere has been shown to be important with respect to cellular senescence, although it may not be detected according to traditional mean telomere length [assessed as the terminal restriction fragment (TRF)] analyses. In the present study, a continuous time window from irradiation was selected to examine changes in the telomere length, including the mean TRF length, percentage of the telomere length, telomerase activity, apoptotic rate, and survival rate in HUVECs from the first day to the fourth day after the administration of a 0.5-Gy dose of irradiation. The mean TRF length in the irradiated HUVECs showed shorter telomere length in first 3 days, but they were not statistically significant. On the other hand, according to the percentage analysis of the telomere length, a decreasing tendency was noted in the longer telomere lengths (9.4–4.4 kb), with a significant increase in the shortest telomeres (4.4–2.3 kb) among the irradiated cells versus the controls from the first day to the third after irradiation; no significant differences were noted on the fourth day. These results suggest that the shortest telomeres are sensitive to the late stage of radiation damage. The proliferation of irradiated cells was suppressed after IR in contrast to the non-irradiated cells. The apoptotic rate was elevated initially both in IR- and non-IR-cells, but that of IR-cells was maintained at an elevated level thereafter in contrast to that of non-IR-cells decreasing promptly. Therefore, a 0.5-Gy dose of IR induces persistent apoptosis leading to an apparent growth arrest of the normal HUVECs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Chiu CP, Harley CB (1997) Replicative senescence and cell immortality: the role of telomeres and telomerase. Proc Soc Exp Biol Med 214:99–106

    Article  PubMed  CAS  Google Scholar 

  2. Goytisolo FA, Samper E, Edmonson S, Taccioli GE, Blasco MA (2001) The absence of the dna-dependent protein kinase catalytic subunit in mice results in anaphase bridges and in increased telomeric fusions with normal telomere length and G-strand overhang. Mol Cell Biol 21:3642–3651

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  3. van Steensel B, Smogorzewska A, de Lange T (1998) TRF2 protects human telomeres from end-to-end fusions. Cell 92:401–413

    Article  PubMed  Google Scholar 

  4. Neuhof D, Ruess A, Wenz F, Weber KJ (2001) Induction of telomerase activity by irradiation in human lymphoblasts. Radiat Res 155:693–697

    Article  PubMed  CAS  Google Scholar 

  5. Hyeon Joo O, Hande MP, Lansdorp PM, Natarajan AT (1998) Induction of telomerase activity and chromosome aberrations in human tumour cell lines following X-irradiation. Mutat Res 401:121–131

    Article  PubMed  CAS  Google Scholar 

  6. Leteurtre F, Li X, Gluckman E, Carosella ED (1997) Telomerase activity during the cell cycle and in gamma-irradiated hematopoietic cells. Leukemia 11:1681–1689

    Article  PubMed  CAS  Google Scholar 

  7. Suzuki K, Mori I, Nakayama Y, Miyakoda M, Kodama S, Watanabe M (2001) Radiation-induced senescence-like growth arrest requires TP53 function but not telomere shortening. Radiat Res 155:248–253

    Article  PubMed  CAS  Google Scholar 

  8. Rubio MA, Kim SH, Campisi J (2002) Reversible manipulation of telomerase expression and telomere length. Implications for the ionizing radiation response and replicative senescence of human cells. J Biol Chem 277:28609–28617

    Article  PubMed  CAS  Google Scholar 

  9. Hayflick L (1965) The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 37:614–636

    Article  PubMed  CAS  Google Scholar 

  10. Jackson SP (2002) Sensing and repairing DNA double-strand breaks. Carcinogenesis 23:687–696

    Article  PubMed  CAS  Google Scholar 

  11. McIlrath J, Bouffler SD, Samper E et al (2001) Telomere length abnormalities in mammalian radiosensitive cells. Cancer Res 61:912–915

    PubMed  CAS  Google Scholar 

  12. Ahmed S, Hodgkin J (2000) MRT-2 checkpoint protein is required for germline immortality and telomere replication in C. elegans. Nature 403:159–164

    Article  PubMed  CAS  Google Scholar 

  13. Lanza V, Pretazzoli V, Olivieri G, Pascarella G, Panconesi A, Negri R (2005) Transcriptional response of human umbilical vein endothelial cells to low doses of ionizing radiation. J Radiat Res 46:265–276

    Article  PubMed  CAS  Google Scholar 

  14. Harley CB, Futcher AB, Greider CW (1990) Telomeres shorten during ageing of human fibroblasts. Nature 345:458–460

    Article  PubMed  CAS  Google Scholar 

  15. Vaziri H, Dragowska W, Allsopp RC, Thomas TE, Harley CB, Lansdorp PM (1994) Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeirc DNA with age. Proc Natl Acad Aci USA 91:9857–9860

    Article  CAS  Google Scholar 

  16. Cherif H, Tarry JL, Ozanne SE, Hales CN (2003) Ageing and telomeres: a study into organ- and gender-specific telomere shortening. Nucl Acid Res 31:1576–1583

    Article  CAS  Google Scholar 

  17. de Lange T, Shiue L, Myers RM et al (1990) Structure and variability of human chromosome ends. Mol Cell Biol 10:518–527

    PubMed  PubMed Central  Google Scholar 

  18. Nagata T, Takada Y, Ono A et al (2008) Elucidation of the mode of interaction in the UP1-telomerase RNA-telomeric DNA ternary complex which serves to recruit telomerase to telomeric DNA and to enhance the telomerase activity. Nucleic Acids Res 36:6816–6824

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  19. Sugano M, Tsuchida K, Maeda T, Makino N (2007) siRNA targeting SHP-1 accelerates angiogenesis in a rat model of hindlimb ischemia. Atherosclerosis 191:33–39

    Article  PubMed  CAS  Google Scholar 

  20. Robles SJ, Adami GR (1998) Agents that cause DNA double strand breaks lead to p16INK4a enrichment and the premature senescence of normal fibroblasts. Oncogene 16:1113–1123

    Article  PubMed  CAS  Google Scholar 

  21. Hemann MT, Strong MA, Hao LY, Greider CW (2001) The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability. Cell 107:67–77

    Article  PubMed  CAS  Google Scholar 

  22. von Zglinicki T (2003) Replicative senescence and the art of counting. Exp Gerontol 38:1259–1264

    Article  Google Scholar 

  23. Ojima M, Hamano H, Suzuki M, Suzuki K, Kodama S, Watanabe M (2004) Delayed induction of telomere instability in normal human fibroblast cells by ionizing radiation. J Radiat Res 45:105–110

    Article  PubMed  Google Scholar 

  24. Kawanishi S, Oikawa S (2004) Mechanism of telomere shortening by oxidative stress. Ann NY Acad Sci 1019:278–284

    Article  PubMed  CAS  Google Scholar 

  25. Przybyszewski WM, Widel M, Rzeszowska-Wolny J (2006) Cardiotoxic consequences of ionizing radiation and anthracyclines. Postepy Hig Med Dosw 60:397–405

    Google Scholar 

  26. Little JB, Lauriston S (2006) Taylor lecture: nontargeted effects of radiation: implications for low-dose exposures. Health Phys 91:416–426

    Article  PubMed  CAS  Google Scholar 

  27. Ogretmen B, Schady D, Usta J et al (2001) Role of ceramide in mediating the inhibition of telomerase activity in A549 human lung adenocarcinoma cells. J Biol Chem 276:24901–24910

    Article  PubMed  CAS  Google Scholar 

  28. Rubio MA, Davalos AR, Campisi J (2004) Telomere length mediates the effects of telomerase on the cellular response to genotoxic stress. Exp Cell Res 298:17–27

    Article  PubMed  CAS  Google Scholar 

  29. Wong KK, Chang S, Weiler SR et al (2000) Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation. Nat Genet 26:85–88

    Article  PubMed  CAS  Google Scholar 

  30. Hande P, Slijepcevic P, Silver A, Bouffler S, van Buul P, Bryant P, Lansdorp P (1999) Elongated telomeres in scid mice. Genomics 56:221–223

    Article  PubMed  CAS  Google Scholar 

  31. Undarmaa B, Kodama S, Suzuki K, Niwa O, Watanabe M (2004) X-ray-induced telomeric instability in Atm-deficient mouse cells. Biochem Biophys Res Commun 315:51–58

    Article  PubMed  CAS  Google Scholar 

  32. Jones KR, Elmore LW, Jackson-Cook C, Demasters G, Povirk LF, Holt SE, Gewirtz DA (2005) p53-Dependent accelerated senescence induced by ionizing radiation in breast tumour cells. Int J Radiat Biol 81:445–458

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported, in part, by the National Natural Science Fund (NSFC) (81170329/H2501), the Ministry of Education, Science, and Culture of Japan (#23590885), the 2012 Health and Labour Sciences Research Grants Comprehensive Research on Life-Style Related Diseases including Cardiovascular Diseases and Diabetes Mellitus.

Author information

Authors and Affiliations

  1. The 309th Hospital of Chinese People’s Liberation Army, Beijing, 100091, China

    Jing-Zhi Guan

  2. Nanlou Neurology Department, Chinese PLA general hospital, Beijing, 100853, China

    Wei Ping Guan

  3. The Division of Cardiovascular, Respiratory and Geriatric Medicine, Kyushu University Beppu Hospital, Beppu, Oita, 874-0838, Japan

    Toyoki Maeda & Naoki Makino

Authors
  1. Jing-Zhi Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wei Ping Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Toyoki Maeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Naoki Makino
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Toyoki Maeda.

Additional information

Jing-Zhi Guan, Wei Ping Guan and Toyoki Maeda have authors equally contributed to this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Guan, JZ., Guan, W.P., Maeda, T. et al. Changes in telomere length distribution in low-dose X-ray-irradiated human umbilical vein endothelial cells. Mol Cell Biochem 396, 129–135 (2014). https://doi.org/10.1007/s11010-014-2149-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-014-2149-5

Keywords

Search

Navigation