DOI QR코드

DOI QR Code

Upregulation of HIF-1α by Hypoxia Protect Neuroblastoma Cells from Apoptosis by Promoting Survivin Expression

  • Zhang, Bo (Department of Physical Medicine and Rehabilitation, Qi Lu Hospital, Medical School of Shandong University) ;
  • Yin, Cui-Ping (Department of Physical Medicine and Rehabilitation, Qi Lu Hospital, Medical School of Shandong University) ;
  • Zhao, Qian (Department of Ultrasound in Medicine, Dongying People's Hospital) ;
  • Yue, Shou-Wei (Department of Physical Medicine and Rehabilitation, Qi Lu Hospital, Medical School of Shandong University)
  • Published : 2014.10.23

Abstract

Apoptosis is one of main types of neural cell death and is reversible and is a major target of therapeutic interventions. However, detailed apoptotic cascades still need to be recognized. In present study, we determined the promotion of HIF-$1{\alpha}$ and survivin in brain samples of a mouse model of hypoxic-ischemia and in neuroblastoma SH-SY5Y cells post hypoxia treatment. Then gain-of-function and loss-of-function strategies were adopted to manipulate the HIF-$1{\alpha}$ in SH-SY5Y cells, and hypoxia-induced survivin upregulation and cell apoptosis were determined. Results demonstrated that the HIF-$1{\alpha}$ and survivin were significantly promoted in a mouse model of hypoxic-ischemia or in SH-SY5Y cells post hypoxia in vitro. Manually upregulated HIF-$1{\alpha}$ could promote the hypoxia-induced survivin upregulation and improve the hypoxia-induced SH-SY5Y cell apoptosis. On the other hand, the HIF-$1{\alpha}$ knockdown by RNAi reduced the hypoxia-induced survivin upregulation and cell apoptosis. Therefore, the present study confirmed the protective role of HIF-$1{\alpha}$ and survivin in the hypoxia-induced SH-SY5Y cell apoptosis, and the survivin upregulation by hypoxia is HIF-$1{\alpha}$-dependent. Promotion of HIF-$1{\alpha}$ and survivin might be a valuable stragegy for therapeutic intervention for hypoxic-ischemic encephalopathy.

Keywords

References

  1. Akakura N, Kobayashi M, Horiuchi I, et al (2001). Constitutive expression of hypoxia-inducible factor-1alpha renders pancreatic cancer cells resistant to apoptosis induced by hypoxia and nutrient deprivation. Cancer Res, 61, 6548-54.
  2. Al-Astani TDT, Shamsuddin SH, Idris FM, et al (2014). Rapamycin and PF4 induce apoptosis by upregulating bax and down-regulating survivin in MNU-induced breast cancer. Asian Pac J Cancer Prev, 15, 3939-44. https://doi.org/10.7314/APJCP.2014.15.9.3939
  3. Altieri DC, Marchisio PC (1999). Survivin apoptosis: an interloper between cell death and cell proliferation in cancer. Lab Invest, 79, 1327-33.
  4. Ambrosini G, Adida C, Altieri DC (1997). A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med, 3, 917-21. https://doi.org/10.1038/nm0897-917
  5. Bai H, Ge S, Lu J, et al (2013). Hypoxia inducible factor-1alphamediated activation of survivin in cervical cancer cells. J Obstet Gynaecol Res, 39, 555-63. https://doi.org/10.1111/j.1447-0756.2012.01995.x
  6. Benchoua A, Guegan C, Couriaud C, et al (2001). Specific caspase pathways are activated in the two stages of cerebral infarction. J Neurosci, 21, 7127-34.
  7. Bonita R, Mendis S, Truelsen T, et al (2004). The global stroke initiative. Lancet Neurol, 3, 391-3. https://doi.org/10.1016/S1474-4422(04)00800-2
  8. Carmeliet P, Dor Y, Herbert JM, et al (1998). Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature, 394, 485-90. https://doi.org/10.1038/28867
  9. Chen B, Yuping S, Ni J (2012). Rapamycin decreases survivin expression to induce NSCLC cell apoptosis under hypoxia through inhibiting HIF-1alpha induction. Mol Biol Rep, 39, 185-91. https://doi.org/10.1007/s11033-011-0724-3
  10. Chen D, Li M, Luo J, Gu W (2003). Direct interactions between HIF-1 alpha and Mdm2 modulate p53 function. J Biol Chem, 278, 13595-8. https://doi.org/10.1074/jbc.C200694200
  11. Christofk HR, Vander HM, Harris MH, et al (2008). The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature, 452, 230-3. https://doi.org/10.1038/nature06734
  12. Cummins EP, Taylor CT (2005). Hypoxia-responsive transcription factors. Pflugers Arch, 450, 363-71. https://doi.org/10.1007/s00424-005-1413-7
  13. Du S, Batis C, Wang H, et al (2014). Understanding the patterns and trends of sodium intake, potassium intake, and sodium to potassium ratio and their effect on hypertension in China. Am J Clin Nutr, 99, 334-43. https://doi.org/10.3945/ajcn.113.059121
  14. Ferrer I, Planas AM (2003). Signaling of cell death and cell survival following focal cerebral ischemia: life and death struggle in the penumbra. J Neuropathol Exp Neurol, 62, 329-39.
  15. Fortugno P, Beltrami E, Plescia J, et al (2003). Regulation of survivin function by Hsp90. Proc Natl Acad Sci USA, 100, 13791-6. https://doi.org/10.1073/pnas.2434345100
  16. Graham SH, Chen J (2001). Programmed cell death in cerebral ischemia. J Cereb Blood Flow Metab, 21, 99-109.
  17. Greijer AE, van der Wall E (2004). The role of hypoxia inducible factor 1 (HIF-1) in hypoxia induced apoptosis. J Clin Pathol, 57, 1009-14. https://doi.org/10.1136/jcp.2003.015032
  18. Grossman D, Kim PJ, Blanc-Brude OP, et al (2001). Transgenic expression of survivin in keratinocytes counteracts UVBinduced apoptosis and cooperates with loss of p53. J Clin Invest, 108, 991-9. https://doi.org/10.1172/JCI13345
  19. Gu D, Reynolds K, Wu X, et al (2002). Prevalence, awareness, treatment, and control of hypertension in china. Hypertension, 40, 920-7. https://doi.org/10.1161/01.HYP.0000040263.94619.D5
  20. He J, Gu D, Wu X, et al (2005). Major causes of death among men and women in China. N Engl J Med, 353, 1124-34. https://doi.org/10.1056/NEJMsa050467
  21. Hoffman WH, Biade S, Zilfou JT, et al (2002). Transcriptional repression of the anti-apoptotic survivin gene by wild type p53. J Biol Chem, 277, 3247-57. https://doi.org/10.1074/jbc.M106643200
  22. Kaelin WJ, Ratcliffe PJ (2008). Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell, 30, 393-402. https://doi.org/10.1016/j.molcel.2008.04.009
  23. Karami H, Baradaran B, Esfahani A, et al (2013). siRNAmediated silencing of survivin inhibits proliferation and enhances etoposide chemosensitivity in acute myeloid leukemia cells. Asian Pac J Cancer Prev, 14, 7719-24. https://doi.org/10.7314/APJCP.2013.14.12.7719
  24. Kato H, Kogure K (1999). Biochemical and molecular characteristics of the brain with developing cerebral infarction. Cell Mol Neurobiol, 19, 93-108. https://doi.org/10.1023/A:1006920725663
  25. Kobayashi K, Hatano M, Otaki M, et al (1999). Expression of a murine homologue of the inhibitor of apoptosis protein is related to cell proliferation. Proc Natl Acad Sci USA, 96, 1457-62. https://doi.org/10.1073/pnas.96.4.1457
  26. Kothari S, Cizeau J, McMillan-Ward E, et al (2003). BNIP3 plays a role in hypoxic cell death in human epithelial cells that is inhibited by growth factors EGF and IGF. Oncogene, 22, 4734-44. https://doi.org/10.1038/sj.onc.1206666
  27. Li G, Chang H, Zhai YP, Xu W (2013). Targeted silencing of inhibitors of apoptosis proteins with siRNAs: a potential anti-cancer strategy for hepatocellular carcinoma. Asian Pac J Cancer Prev, 14, 4943-52.
  28. Li Y, Xia ZL, Chen LB (2011). HIF-1-alpha and survivin involved in the anti-apoptotic effect of 2ME2 after global ischemia in rats. Neurol Res, 33, 583-92. https://doi.org/10.1179/1743132810Y.0000000013
  29. Licausi F, Weits DA, Pant BD, et al (2011). Hypoxia responsive gene expression is mediated by various subsets of transcription factors and miRNAs that are determined by the actual oxygen availability. New Phytol, 190, 442-56. https://doi.org/10.1111/j.1469-8137.2010.03451.x
  30. Linnik MD, Zobrist RH, Hatfield MD (1993). Evidence supporting a role for programmed cell death in focal cerebral ischemia in rats. Stroke, 24, 2002-8, 2008-9.
  31. Livak KJ, Schmittgen TD (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2 [-Delta Delta C (T)] Method. Methods, 25, 402-8. https://doi.org/10.1006/meth.2001.1262
  32. McBride CA, Hale SA, Subramanian M, et al (2014). The relationship of a family history for hypertension, myocardial infarction, or stroke with cardiovascular physiology in young women. Reprod Sci, 21, 509-16. https://doi.org/10.1177/1933719113503402
  33. Moritz W, Meier F, Stroka DM, et al (2002). Apoptosis in hypoxic human pancreatic islets correlates with HIF-1alpha expression. FASEB J, 16, 745-7.
  34. Nakka VP, Gusain A, Mehta SL, Raghubir R (2008). Molecular mechanisms of apoptosis in cerebral ischemia: multiple neuroprotective opportunities. Mol Neurobiol, 37, 7-38. https://doi.org/10.1007/s12035-007-8013-9
  35. Newcomb JD, Ajmo CJ, Sanberg CD, et al (2006). Timing of cord blood treatment after experimental stroke determines therapeutic efficacy. Cell Transplant, 15, 213-23. https://doi.org/10.3727/000000006783982043
  36. Northington FJ, Ferriero DM, Flock DL, Martin LJ (2001). Delayed neurodegeneration in neonatal rat thalamus after hypoxia-ischemia is apoptosis. J Neurosci, 21, 1931-8.
  37. Noton EA, Colnaghi R, Tate S, et al (2006). Molecular analysis of survivin isoforms: evidence that alternatively spliced variants do not play a role in mitosis. J Biol Chem, 281, 1286-95. https://doi.org/10.1074/jbc.M508773200
  38. O'Connor DS, Grossman D, Plescia J, et al (2000). Regulation of apoptosis at cell division by p34cdc2 phosphorylation of survivin. Proc Natl Acad Sci USA, 97, 13103-7. https://doi.org/10.1073/pnas.240390697
  39. Peng XH, Karna P, Cao Z, et al (2006). Cross-talk between epidermal growth factor receptor and hypoxia-inducible factor-1alpha signal pathways increases resistance to apoptosis by up-regulating survivin gene expression. J Biol Chem, 281, 25903-14. https://doi.org/10.1074/jbc.M603414200
  40. Ping W, Jiang WY, Chen WS, et al (2013). Expression and significance of hypoxia inducible factor-1alpha and lysyl oxidase in non-small cell lung cancer. Asian Pac J Cancer Prev, 14, 3613-8. https://doi.org/10.7314/APJCP.2013.14.6.3613
  41. Piret JP, Mottet D, Raes M, Michiels C (2002). Is HIF-1alpha a pro-or an anti-apoptotic protein? Biochem Pharmacol, 64, 889-92. https://doi.org/10.1016/S0006-2952(02)01155-3
  42. Pouyssegur J, Dayan F, Mazure NM (2006). Hypoxia signalling in cancer and approaches to enforce tumour regression. Nature, 441, 437-43. https://doi.org/10.1038/nature04871
  43. Rubio N, Garcia-Segura LM, Arevalo MA (2012). Survivin prevents apoptosis by binding to caspase-3 in astrocytes infected with the BeAn strain of Theiler's murine encephalomyelitis virus. J Neurovirol, 18, 354-63. https://doi.org/10.1007/s13365-012-0112-3
  44. Savitz DA, Danilack VA, Elston B, Lipkind HS (2014). Pregnancy-induced hypertension and diabetes and the risk of cardiovascular disease, stroke, and diabetes hospitalization in the year following delivery. Am J Epidemiol, 180, 41-4. https://doi.org/10.1093/aje/kwu118
  45. Schimmer AD (2004). Inhibitor of apoptosis proteins: translating basic knowledge into clinical practice. Cancer Res, 64, 7183-90. https://doi.org/10.1158/0008-5472.CAN-04-1918
  46. Semenza GL (2003). Targeting HIF-1 for cancer therapy. Nat Rev Cancer, 3, 721-32. https://doi.org/10.1038/nrc1187
  47. Shankar SL, Mani S, O'Guin KN, et al (2001). Survivin inhibition induces human neural tumor cell death through caspaseindependent and -dependent pathways. J Neurochem, 79, 426-36.
  48. Sheldon RA, Sedik C, Ferriero DM (1998). Strain-related brain injury in neonatal mice subjected to hypoxia-ischemia. Brain Res, 810, 114-22. https://doi.org/10.1016/S0006-8993(98)00892-0
  49. Shin S, Sung BJ, Cho YS, et al (2001). An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and-7. Biochemistry-Us, 40, 1117-23. https://doi.org/10.1021/bi001603q
  50. Sommer KW, Schamberger CJ, Schmidt GE, et al (2003). Inhibitor of apoptosis protein (IAP) survivin is upregulated by oncogenic c-H-Ras. Oncogene, 22, 4266-80. https://doi.org/10.1038/sj.onc.1206509
  51. Sun Z, Zheng L, Wei Y, et al (2007). The prevalence of prehypertension and hypertension among rural adults in Liaoning province of China. Clin Cardiol, 30, 183-7. https://doi.org/10.1002/clc.20073
  52. Tarnawski AS, Szabo I (2001). Apoptosis-programmed cell death and its relevance to gastrointestinal epithelium: survival signal from the matrix. Gastroenterology, 120, 294-9. https://doi.org/10.1053/gast.2001.21402
  53. Vaira V, Lee CW, Goel HL, et al (2007). Regulation of survivin expression by IGF-1/mTOR signaling. Oncogene, 26, 2678-84. https://doi.org/10.1038/sj.onc.1210094
  54. Van Antwerp DJ, Martin SJ, Verma IM, Green DR (1998). Inhibition of TNF-induced apoptosis by NF-kappa B. Trends Cell Biol, 8, 107-11. https://doi.org/10.1016/S0962-8924(97)01215-4
  55. Wang GL, Jiang BH, Rue EA, Semenza GL (1995). Hypoxiainducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular $O_2$ tension. Proc Natl Acad Sci USA, 92, 5510-4. https://doi.org/10.1073/pnas.92.12.5510
  56. Whiteley W, Tseng MC, Sandercock P (2008). Blood biomarkers in the diagnosis of ischemic stroke: a systematic review. Stroke, 39, 2902-9. https://doi.org/10.1161/STROKEAHA.107.511261
  57. You L, He B, Xu Z, et al (2004). Inhibition of Wnt-2-mediated signaling induces programmed cell death in non-small-cell lung cancer cells. Oncogene, 23, 6170-4. https://doi.org/10.1038/sj.onc.1207844
  58. Zhao J, Tenev T, Martins LM, et al (2000). The ubiquitinproteasome pathway regulates survivin degradation in a cell cycle-dependent manner. J Cell Sci, 113, 4363-71.

Cited by

  1. Upregulation of HIF-1α protects neuroblastoma cells from hypoxia-induced apoptosis in a RhoA-dependent manner vol.12, pp.5, 2015, https://doi.org/10.3892/mmr.2015.4267
  2. Hypoxia-inducible factor 1 alpha is a poor prognostic factor and potential therapeutic target in malignant peripheral nerve sheath tumor vol.12, pp.5, 2017, https://doi.org/10.1371/journal.pone.0178064
  3. Cell death-based treatment of neuroblastoma vol.9, pp.2, 2018, https://doi.org/10.1038/s41419-017-0060-1
  4. The Synergistic Combination of Everolimus and Paroxetine Exerts Post-ischemic Neuroprotection In Vitro vol.38, pp.7, 2018, https://doi.org/10.1007/s10571-018-0605-6