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Han N, Kim YJ, Park SM, et al. Repeated Glucose Deprivation/Reperfusion Induced PC-12 Cell Death through the Involvement of FOXO Transcription Factor. Diabetes Metab J. 2016;40(5):396-405doi: 10.4093/dmj.2016.40.5.396.
Han, N., Kim, Y. J., Park, S. M., Kim, S. M., Lee, J. S., Jung, H. S., Lee, E. J., Kim, T. K., Kim, T. N., Kwon, M. J., Lee, S. H., Kim, M. K., Rhee, B. D., & Park, J. H. (2016). Repeated Glucose Deprivation/Reperfusion Induced PC-12 Cell Death through the Involvement of FOXO Transcription Factor. Diabetes & metabolism journal, 40(5), 396-405. https://doi.org/10.4093/dmj.2016.40.5.396
Han, Na, et al. "Repeated Glucose Deprivation/Reperfusion Induced PC-12 Cell Death through the Involvement of FOXO Transcription Factor." Diabetes & metabolism journal vol. 40,5 (2016): 396-405. doi: https://doi.org/10.4093/dmj.2016.40.5.396
Han N, Kim YJ, Park SM, Kim SM, Lee JS, Jung HS, Lee EJ, Kim TK, Kim TN, Kwon MJ, Lee SH, Kim MK, Rhee BD, Park JH. Repeated Glucose Deprivation/Reperfusion Induced PC-12 Cell Death through the Involvement of FOXO Transcription Factor. Diabetes Metab J. 2016 Oct;40(5):396-405. doi: 10.4093/dmj.2016.40.5.396. Epub 2016 Sep 01. PMID: 27766247; PMCID: PMC5069396.
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Diabetes Metab J. 2016 Oct;40(5):396-405. doi: 10.4093/dmj.2016.40.5.396. Epub 2016 Sep 01.

Repeated Glucose Deprivation/Reperfusion Induced PC-12 Cell Death through the Involvement of FOXO Transcription Factor.

Diabetes & metabolism journal

Na Han, You Jeong Kim, Su Min Park, Seung Man Kim, Ji Suk Lee, Hye Sook Jung, Eun Ju Lee, Tae Kyoon Kim, Tae Nyun Kim, Min Jeong Kwon, Soon Hee Lee, Mi-Kyung Kim, Byoung Doo Rhee, Jeong Hyun Park

Affiliations

  1. Division of Endocrinology and Metabolism, Department of Internal Medicine, Onhospital, Busan, Korea.
  2. Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University College of Medicine, Busan, Korea.
  3. Paik Institute for Clinical Research, Molecular Therapy Lab, Inje University, Busan, Korea.
  4. Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University College of Medicine, Busan, Korea.; Paik Institute for Clinical Research, Molecular Therapy Lab, Inje University, Busan, Korea.

PMID: 27766247 PMCID: PMC5069396 DOI: 10.4093/dmj.2016.40.5.396

Abstract

BACKGROUND: Cognitive impairment and brain damage in diabetes is suggested to be associated with hypoglycemia. The mechanisms of hypoglycemia-induced neural death and apoptosis are not clear and reperfusion injury may be involved. Recent studies show that glucose deprivation/reperfusion induced more neuronal cell death than glucose deprivation itself. The forkhead box O (FOXO) transcription factors are implicated in the regulation of cell apoptosis and survival, but their role in neuronal cells remains unclear. We examined the role of FOXO transcription factors and the involvement of the phosphatidylinositol 3-kinase (PI3K)/Akt and apoptosis-related signaling pathways in PC-12 cells exposed to repeated glucose deprivation/reperfusion.

METHODS: PC-12 cells were exposed to control (Dulbecco's Modified Eagle Medium [DMEM] containing 25 mM glucose) or glucose deprivation/reperfusion (DMEM with 0 mM glucose for 6 hours and then DMEM with 25 mM glucose for 18 hours) for 5 days. MTT assay and Western blot analysis were performed for cell viability, apoptosis, and the expression of survival signaling pathways. FOXO3/4',6-diamidino-2-phenylindole staining was done to ascertain the involvement of FOXO transcription factors in glucose deprivation/reperfusion conditions.

RESULTS: Compared to PC-12 cells not exposed to hypoglycemia, cells exposed to glucose deprivation/reperfusion showed a reduction of cell viability, decreased expression of phosphorylated Akt and Bcl-2, and an increase of cleaved caspase-3 expression. Of note, FOXO3 protein was localized in the nuclei of glucose deprivation/reperfusion cells but not in the control cells.

CONCLUSION: Repeated glucose deprivation/reperfusion caused the neuronal cell death. Activated FOXO3 via the PI3K/Akt pathway in repeated glucose deprivation/reperfusion was involved in genes related to apoptosis.

Keywords: Apoptosis; Forkhead box O; PC-12 cell; Phosphatidylinositol 3-kinase/Akt pathway; Reperfusion

Conflict of interest statement

No potential conflict of interest relevant to this article was reported.

References

  1. Metab Brain Dis. 2004 Dec;19(3-4):169-75 - PubMed
  2. Neurosci Lett. 2011 Mar 29;492(1):23-8 - PubMed
  3. Neuroscience. 1999;90(4):1325-38 - PubMed
  4. Cell Mol Biol (Noisy-le-grand). 2012 Oct 10;Suppl.58:OL1780-5 - PubMed
  5. Acta Diabetol. 2012 Dec;49 Suppl 1:S81-5 - PubMed
  6. Nat Rev Cancer. 2007 Nov;7(11):847-59 - PubMed
  7. Cell Mol Neurobiol. 2014 Nov;34(8):1103-9 - PubMed
  8. Neurology. 2011 Oct 4;77(14 ):1351-6 - PubMed
  9. Oncogene. 2005 Nov 14;24(50):7410-25 - PubMed
  10. J Neurosci. 1997 Feb 1;17 (3):1046-54 - PubMed
  11. Arch Neurol. 2005 Oct;62(10):1539-44 - PubMed
  12. Cell Mol Neurobiol. 2011 Nov;31(8):1187-94 - PubMed
  13. Brain Res. 2009 Jul 14;1280:186-94 - PubMed
  14. J Neurochem. 1997 Jul;69(1):273-84 - PubMed
  15. Am J Physiol Cell Physiol. 2006 May;290(5):C1373-84 - PubMed
  16. J Clin Invest. 2007 Apr;117(4):910-8 - PubMed
  17. Cell Mol Neurobiol. 2008 Dec;28(8):1067-78 - PubMed
  18. Neurology. 2010 Aug 31;75(9):764-70 - PubMed
  19. Mol Biol Rep. 2012 Jun;39(6):6495-503 - PubMed
  20. Free Radic Biol Med. 2001 Nov 15;31(10 ):1216-27 - PubMed
  21. Neurochem Int. 2013 Oct;63(4):331-43 - PubMed
  22. Neurosci Lett. 2006 May 15;399(1-2):111-4 - PubMed
  23. JAMA. 2009 Apr 15;301(15):1565-72 - PubMed
  24. Neurol Sci. 2014 Jun;35(6):875-81 - PubMed
  25. Cell Mol Neurobiol. 2010 May;30(4):591-8 - PubMed
  26. Neuroscience. 2010 Jun 2;167(4):1057-69 - PubMed
  27. J Biol Chem. 2003 Sep 19;278(38):35959-67 - PubMed
  28. Neurology. 2010 Sep 28;75(13):1195-202 - PubMed
  29. J Neurosci Res. 2015 Jan;93(1):140-8 - PubMed
  30. Neuroscience. 1999 Jan;88(1):57-67 - PubMed
  31. Lancet Neurol. 2006 Jan;5(1):64-74 - PubMed
  32. Arterioscler Thromb Vasc Biol. 2012 Mar;32(3):712-20 - PubMed
  33. Cell. 1999 Mar 19;96(6):857-68 - PubMed
  34. Diabetes Care. 2009 Feb;32(2):221-6 - PubMed
  35. J Neurochem. 1986 Jul;47(1):178-84 - PubMed
  36. Oncogene. 2008 Apr 7;27(16):2300-11 - PubMed
  37. J Cereb Blood Flow Metab. 1984 Jun;4(2):187-93 - PubMed
  38. Acta Neuropathol. 1984;62(3):201-8 - PubMed

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