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Domazetovic V, Fontani F, Marcucci G, et al. Estrogen inhibits starvation-induced apoptosis in osteocytes by a redox-independent process involving association of JNK and glutathione S-transferase P1-1. FEBS Open Bio. 2017;7(5):705-718doi: 10.1002/2211-5463.12216.
Domazetovic, V., Fontani, F., Marcucci, G., Iantomasi, T., Brandi, M. L., & Vincenzini, M. T. (2017). Estrogen inhibits starvation-induced apoptosis in osteocytes by a redox-independent process involving association of JNK and glutathione S-transferase P1-1. FEBS open bio, 7(5), 705-718. https://doi.org/10.1002/2211-5463.12216
Domazetovic, Vladana, et al. "Estrogen inhibits starvation-induced apoptosis in osteocytes by a redox-independent process involving association of JNK and glutathione S-transferase P1-1." FEBS open bio vol. 7,5 (2017): 705-718. doi: https://doi.org/10.1002/2211-5463.12216
Domazetovic V, Fontani F, Marcucci G, Iantomasi T, Brandi ML, Vincenzini MT. Estrogen inhibits starvation-induced apoptosis in osteocytes by a redox-independent process involving association of JNK and glutathione S-transferase P1-1. FEBS Open Bio. 2017 Apr 05;7(5):705-718. doi: 10.1002/2211-5463.12216. eCollection 2017 May. PMID: 28469982; PMCID: PMC5407897.
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FEBS Open Bio. 2017 Apr 05;7(5):705-718. doi: 10.1002/2211-5463.12216. eCollection 2017 May.

Estrogen inhibits starvation-induced apoptosis in osteocytes by a redox-independent process involving association of JNK and glutathione S-transferase P1-1.

FEBS open bio

Vladana Domazetovic, Filippo Fontani, Gemma Marcucci, Teresa Iantomasi, Maria Luisa Brandi, Maria Teresa Vincenzini

Affiliations

  1. Department of Biomedical, Experimental and Clinical Sciences "Mario Serio" (Biochemistry section) University of Florence Italy.
  2. Department of Surgery and Translational Medicine (Endocrinology Section) University of Florence Italy.

PMID: 28469982 PMCID: PMC5407897 DOI: 10.1002/2211-5463.12216

Abstract

Estrogen deficiency causes bone loss as a result of microdamage, oxidative stress, and osteocyte apoptosis. A relationship between oxidative stress-induced apoptosis, c-Jun N-terminal kinase (JNK) activation, and expression of factors involved in bone remodeling has been demonstrated in osteocytes. However, the molecular regulation of these events in osteocytes treated with 17β-estradiol (17β-E2) remains unexplored. The MLO-Y4 murine osteocyte-like cell line was used as a model to study starvation-induced apoptosis and ROS production during 17β-E2 treatment. Expression of glutathione S-transferase P1-1 (GSTP1-1), receptor activator kB ligand (RANKL), osteoprotegerin (OPG), sclerostin, and kinases activation were measured by western blot. In addition, the GSTP1-1/JNK association was assessed by immunoprecipitation, and GSTP1-1 involvement in the osteocyte response to 17β-E2 was detected by specific siRNA transfection. 17β-E2 prevents starvation-induced apoptosis (DNA fragmentation and caspase activation), the increase in sclerostin expression and the RANKL/OPG ratio, which are all related to JNK activation due to oxidative stress in osteocytes. This occurs through GSTP1-1 overexpression, which can inhibit JNK activation by formation of a GSTP1-1/JNK complex. No early antioxidant action of 17β-E2 has been found but the estrogen effect is similar to N-acetylcysteine which, by increasing the intracellular redox state, maintains JNK bound to GSTP1-1. Thus, the antiapoptotic and osteogenic effect of 17β-E2 in MLO-Y4 occurs by a redox-independent process involving GSTP1-1/JNK association. This study clarifies at molecular level the effect of 17β-E2 on osteocyte activity and identifies a possible role of GSTP1-1 and JNK activity in bone remodeling and repair mechanisms.

Keywords: GSTP1‐1 expression; JNK activity; RANKL/OPG ratio; estrogen; osteocyte apoptosis

References

  1. Eur J Morphol. 2005 Feb-Apr;42(1-2):91-8 - PubMed
  2. Osteoporos Int. 2014 Dec;25(12):2685-700 - PubMed
  3. Clin Chem Lab Med. 2008;46(11):1550-5 - PubMed
  4. J Bone Miner Res. 2012 Mar;27(3):637-44 - PubMed
  5. J Clin Endocrinol Metab. 2000 Aug;85(8):2907-12 - PubMed
  6. EMBO J. 2008 Feb 6;27(3):535-45 - PubMed
  7. Am J Physiol Cell Physiol. 2013 Jan 15;304(2):C170-9 - PubMed
  8. Biochem Biophys Res Commun. 2004 Aug 6;320(4):1163-8 - PubMed
  9. Bone. 2013 Jun;54(2):296-306 - PubMed
  10. J Midlife Health. 2013 Jul;4(3):140-6 - PubMed
  11. Calcif Tissue Int. 2015 Apr;96(4):335-46 - PubMed
  12. Bone. 2007 Mar;40(3):674-84 - PubMed
  13. J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Apr 15;1019:29-44 - PubMed
  14. Bone. 2011 Feb;48(2):182-8 - PubMed
  15. J Cell Biochem. 2000 Apr;77(4):645-53 - PubMed
  16. Aging Cell. 2005 Jun;4(3):113-8 - PubMed
  17. Lancet. 2002 May 18;359(9319):1761-7 - PubMed
  18. J Bone Miner Res. 1997 Dec;12(12):2014-23 - PubMed
  19. Am J Pathol. 2009 Oct;175(4):1564-73 - PubMed
  20. Endocrinology. 2005 Feb;146(2):728-35 - PubMed
  21. Nat Rev Endocrinol. 2013 Dec;9(12):699-712 - PubMed
  22. Osteoporos Int. 2010 Sep;21(9):1457-69 - PubMed
  23. FEBS J. 2009 Mar;276(5):1255-65 - PubMed
  24. J Bone Miner Res. 2002 Nov;17(11):2030-7 - PubMed
  25. Free Radic Biol Med. 2015 Nov;88(Pt B):466-80 - PubMed
  26. J Bone Miner Res. 2011 Jan;26(1):27-34 - PubMed
  27. Cell Death Differ. 2010 Sep;17(9):1373-80 - PubMed
  28. Biochem Biophys Res Commun. 2004 Jan 30;314(1):197-207 - PubMed
  29. Biomed Res Int. 2014;2014:569563 - PubMed
  30. Menopause. 2013 Mar;20(3):342-53 - PubMed
  31. Biochim Biophys Acta. 2003 May 12;1640(2-3):113-8 - PubMed
  32. EMBO J. 1999 Mar 1;18(5):1321-34 - PubMed
  33. J Biol Chem. 2012 Jan 6;287(2):978-88 - PubMed
  34. Mol Med Rep. 2013 Feb;7(2):555-8 - PubMed
  35. J Cell Biochem. 2011 Sep;112(9):2412-23 - PubMed
  36. Redox Biol. 2013 Jun 19;1:340-6 - PubMed
  37. J Bone Miner Res. 2010 Apr;25(4):769-81 - PubMed
  38. Bone. 2008 Apr;42(4):606-15 - PubMed
  39. Bone. 2007 Mar;40(3):627-37 - PubMed
  40. J Clin Endocrinol Metab. 2014 Jan;99(1):E81-8 - PubMed
  41. J Basic Clin Physiol Pharmacol. 2007;18(2):115-27 - PubMed
  42. Calcif Tissue Int. 2011 Oct;89(4):327-34 - PubMed
  43. Cell. 2000 Oct 13;103(2):239-52 - PubMed
  44. Bone. 2013 Jun;54(2):264-71 - PubMed
  45. Bone. 2009 Jun;44(6):1026-33 - PubMed
  46. J Biol Chem. 2015 Dec 25;290(52):30866-78 - PubMed
  47. Bone. 2014 Jul;64:132-7 - PubMed
  48. Biochim Biophys Acta. 2011 Apr;1810(4):446-56 - PubMed
  49. Trends Endocrinol Metab. 2012 Nov;23(11):576-81 - PubMed
  50. FEBS J. 2013 Feb;280(3):867-79 - PubMed
  51. J Biol Chem. 2007 Sep 14;282(37):27285-97 - PubMed
  52. Odontology. 2005 Sep;93(1):16-23 - PubMed
  53. J Bone Miner Res. 2011 Feb;26(2):229-38 - PubMed
  54. Osteoporos Int. 2013 Jun;24(6):1771-89 - PubMed

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