Log in

Hypoxia-induced apoptosis in endothelial cells and embryonic stem cells

  • Published:
Apoptosis Aims and scope Submit manuscript

Background: To evaluate the influence of hypoxia and molecular events in endothelial and embryonic stem cells.

Materials and Methods: Human umbilical vein endothelial cells (HUVECs) and mouse embryoid body (EB) cells were subjected to hypoxic conditions for different time courses. DNA fragmentation assay, quantification of apoptotic cells by TUNEL assay measured by flowcytometry, and Western blot analysis for the molecular events of apoptosis were performed.

Results: DNA fragmentation could be identified under hypoxic conditions in HUVECs and mouse EBs. The DNA fragmentation increased when the hypoxic interval was extended.

In situ internucleosomal DNA fragmentation-TUNEL assay also found that the percentages of apoptotic cells increased gradually in HUVECs and mouse EBs when the hypoxic interval was extended. Furthermore, the levels of expression of p53 and Bax both increased in hypoxic conditions.

Conclusions: Hypoxia increases both HUVEC and mouse EB apoptosis, which is associated with increase in p53/Bax expression.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Brazil)

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Kajii T, Ferrier A, Niikawa N, Takahara H, Ohama K, Avirachan S. Anatomic and chromosomal anomalies in 639 spontaneous abortuses. Hum Genet 1980; 55: 87–98.

    Article  PubMed  Google Scholar 

  2. Simpson JL. Genes, chromosomes, and reproductive failure. Fertil Steril 1980; 33: 107–116.

    PubMed  Google Scholar 

  3. Laurini R. Fetal brain pathology. In: Krujak A CF, ed. The Fetus as a Patient. Carnforth, UK: Parthenon, 1994: 89–106.

  4. Pearlstone M, Baxi L. Subchorionic hematoma: A review. Obstet Gynecol Surv 1993; 48: 65–68.

    PubMed  Google Scholar 

  5. Nyberg DA, Cyr DR, Mack LA, Wilson DA, Shuman WP. Sonographic spectrum of placental abruption. AJR Am J Roentgenol 1987; 148: 161–164.

    PubMed  Google Scholar 

  6. Granger JP, Alexander BT, Llinas MT, Bennett WA, Khalil RA. Pathophysiology of preeclampsia: linking placental ischemia/hypoxia with microvascular dysfunction. Microcirculation 2002; 9: 147–160.

    Article  PubMed  Google Scholar 

  7. Carmeliet P, Dor Y, Herbert JM, et al. Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature 1998; 394: 485–490.

    Article  PubMed  Google Scholar 

  8. Stempien-Otero A, Karsan A, Cornejo CJ, et al. Mechanisms of hypoxia-induced endothelial cell death. Role of p53 in apoptosis. J Biol Chem 1999; 274: 8039–8045.

    Article  PubMed  Google Scholar 

  9. Hoshi H, McKeehan WL. Brain- and liver cell-derived factors are required for growth of human endothelial cells in serum-free culture. Proc Natl Acad Sci USA 1984; 81: 6413–6417.

    PubMed  Google Scholar 

  10. Kauma S, Takacs P, Scordalakes C, Walsh S, Green K, Peng T. Increased endothelial monocyte chemoattractant protein-1 and interleukin-8 in preeclampsia. Obstet Gynecol 2002; 100: 706–714.

    Article  PubMed  Google Scholar 

  11. Muller AM, Cronen C, Muller KM, Kirkpatrick CJ. Comparative analysis of the reactivity of human umbilical vein endothelial cells in organ and monolayer culture. Pathobiology 1999; 67: 99–107.

    Article  PubMed  Google Scholar 

  12. Keller GM. In vitro differentiation of embryonic stem cells. Curr Opin Cell Biol 1995; 7: 862–869.

    Article  PubMed  Google Scholar 

  13. Shimizu S, Eguchi Y, Kamiike W, et al. Induction of apoptosis as well as necrosis by hypoxia and predominant prevention of apoptosis by Bcl-2 and Bcl-XL. Cancer Res 1996; 56: 2161–2166.

    PubMed  Google Scholar 

  14. Itano Y, Ito A, Uehara T, Nomura Y. Regulation of Bcl-2 protein expression in human neuroblastoma SH-SY5Y cells: Positive and negative effects of protein kinases C and A, respectively. J Neurochem 1996; 67: 131–137.

    PubMed  Google Scholar 

  15. Cheng WF, Hung CF, Chai CY, et al. Tumor-specific immunity and antiangiogenesis generated by a DNA vaccine encoding calreticulin linked to a tumor antigen. J Clin Invest 2001; 108: 669–678.

    Article  PubMed  Google Scholar 

  16. Cheng WF, Hung CF, Hsu KF, et al. Cancer immunotherapy using Sindbis virus replicon particles encoding a VP22-antigen fusion. Hum Gene Ther 2002; 13: 553–568.

    Article  PubMed  Google Scholar 

  17. Jennings RB, Ganote CE, Reimer KA. Ischemic tissue injury. Am J Pathol 1975; 81: 179–198.

    PubMed  Google Scholar 

  18. Harrison-Shostak DC, Lemasters JJ, Edgell CJ, Herman B. Role of ICE-like proteases in endothelial cell hypoxic and reperfusion injury. Biochem Biophys Res Commun 1997; 231: 844–847.

    Article  PubMed  Google Scholar 

  19. Muschel RJ, Bernhard EJ, Garza L, McKenna WG, Koch CJ. Induction of apoptosis at different oxygen tensions: evidence that oxygen radicals do not mediate apoptotic signaling. Cancer Res 1995; 55: 995–998.

    PubMed  Google Scholar 

  20. Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature 1981; 292: 154–156.

    PubMed  Google Scholar 

  21. Martin GR. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA 1981; 78: 7634–7638.

    PubMed  Google Scholar 

  22. Risau W, Sariola H, Zerwes HG, et al. Vasculogenesis and angiogenesis in embryonic-stem-cell-derived embryoid bodies. Development 1988; 102: 471–478.

    PubMed  Google Scholar 

  23. Wang R, Clark R, Bautch VL. Embryonic stem cell-derived cystic embryoid bodies form vascular channels: an in vitro model of blood vessel development. Development 1992; 114: 303–316.

    PubMed  Google Scholar 

  24. Lee YJ, Kang IJ, Bunger R, Kang YH. Mechanisms of pyruvate inhibition of oxidant-induced apoptosis in human endothelial cells. Microvasc Res 2003; 66: 91–101.

    Article  PubMed  Google Scholar 

  25. Aoki M, Nata T, Morishita R, et al. Endothelial apoptosis induced by oxidative stress through activation of NF-kappaB: antiapoptotic effect of antioxidant agents on endothelial cells. Hypertension 2001; 38: 48–55.

    PubMed  Google Scholar 

  26. Chen YH, Wu HL, Chen CK, Huang YH, Yang BC, Wu LW. Angiostatin antagonizes the action of VEGF-A in human endothelial cells via two distinct pathways. Biochem Biophys Res Commun 2003; 310: 804–810.

    Article  PubMed  Google Scholar 

  27. Stempien-Otero A, Karsan A, Cornejo CJ, et al. Mechanisms of hypoxia-induced endothelial cell death. Role of p53 in apoptosis. J Biol Chem 1999; 274: 8039–8045.

    Article  PubMed  Google Scholar 

  28. Levy R, Smith SD, Chandler K, Sadovsky Y, Nelson DM. Apoptosis in human cultured trophoblasts is enhanced by hypoxia and diminished by epidermal growth factor. Am J Physiol Cell Physiol 2000; 278: C982–988.

    PubMed  Google Scholar 

  29. Alarcon RM, Denko NC, Giaccia AJ. Genetic determinants that influence hypoxia-induced apoptosis. Novartis Found Symp 2001; 240: 115–128; discussion 128–132.

    Google Scholar 

  30. Shen Y, White E. p53-dependent apoptosis pathways. Adv Cancer Res 2001; 82: 55–84.

    PubMed  Google Scholar 

  31. Harris AL. Hypoxia–a key regulatory factor in tumour growth. Nature Rev Cancer 2002; 2: 38–47.

    Article  Google Scholar 

  32. Shen Y, White E. p53-dependent apoptosis pathways. Adv Cancer Res 2001; 82: 55–84.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to W. F. Cheng.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, C.N., Cheng, W.F., Chang, M.C. et al. Hypoxia-induced apoptosis in endothelial cells and embryonic stem cells. Apoptosis 10, 887–894 (2005). https://doi.org/10.1007/s10495-005-2946-0

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10495-005-2946-0

Keywords

Navigation