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Effect of Some Growth Factors on Tissue Transglutaminase Overexpression Induced by β-Amyloid in Olfactory Ensheathing Cells

Abstract

Herein, we assessed in a particular glial cell type, called olfactory ensheathing cells (OECs), the effect of some growth factors (GFs) on tissue transglutaminase (TG2) overexpression induced by amyloid-beta (Aβ) with native full-length peptide 1–42 or by fragments, 25–35 or 35–25, as control. Previously, we demonstrated that TG2 overexpression induced by some stressors was down-regulated by GFs exposure in OECs. To monitor cell viability, an MTT test was used, while TG2 expression was examined using immunocytochemical and Western blot analysis. We also considered the involvement of the TG2-mediated apoptotic pathway. Vimentin expression was evaluated as well. Reactive oxygen species and reduced glutathione levels were utilized to test the oxidative intracellular status. Lactate dehydrogenase released into the medium, as a marker of necrotic cell death, was evaluated. We found that in OECs exposed to Aβ(1–42) or Aβ(25–35) for 24 h, TG2 expression increased, and we observed that the protein appeared prevalently localized in the cytosol. The pre-treatment with GFs, basic fibroblast growth factor (bFGF) or glial-derived neurotrophic factor (GDNF), down-regulated the TG2 level, which was prevalently limited to the nuclear compartment. Vimentin expression and caspase cleavage showed a significant enhancement in Aβ(1–42) and Aβ(25–35) exposed cells. The pre-treatment with bFGF or GDNF was able to restore the levels of the proteins to control values, and the intracellular oxidative status modified by the exposure to Aβ(1–42) or Aβ(25–35). Our data suggest that both bFGF or GDNF could be an innovative mechanism to contrast TG2 expression, which plays a key role in Alzheimer’s disease.

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References

  1. Lorand L, Graham RM (2003) Transglutaminases: crosslinking enzymes with pleiotropic functions. Nat Rev Mol Cell Biol 4:140–156

    CAS  Article  PubMed  Google Scholar 

  2. Hasegawa G, Suwa M, Ichikawa Y, Ohtsuka T, Kumagai S, Kikuchi M, Sato Y, Saito Y (2003) A novel function of tissue-type transglutaminase: protein disulphide isomerase. Biochem J 373:793–803

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. Nakaoka H, Perez DM, Baek KJ, Das T, Husain A, Misono K, Im MJ, Graham RM (1994) Gh: a GTP-binding protein with transglutaminase activity and receptor signaling function. Science 264:1593–1596

    CAS  Article  PubMed  Google Scholar 

  4. Zhang J, Wang S, Huang W, Bennett DA, Dickson DW, Wang D, Wang R (2015) Tissue transglutaminase and its product Isopeptide are increased in Alzheimer’s disease and APPswe/PS1dE9 double transgenic mice brains. Mol Neurobiol. doi:10.1007/s12035-015-9413-x

    Google Scholar 

  5. Wilhelmus MM, Grunber SC, Bol JG, van Dam AM, Hoozemans JJ, Rozemuller AJ, Drukarch B (2009) Transglutaminases and transglutaminase-catalyzed cross-links colocalize with the pathological lesions in Alzheimer’s disease brain. Brain Pathol 19:612–622

    CAS  Article  PubMed  Google Scholar 

  6. Zhou WW, Lu S, Su YJ, Xue D, Yu XL, Wang SW, Zhang H, Xu PX et al (2014) Decreasing oxidative stress and neuroinflammation with a multifunctional peptide rescues memory deficits in mice with Alzheimer disease. Free Radic Biol Mec 74:50–63

    CAS  Article  Google Scholar 

  7. Campisi A, Spatuzza M, Russo A, Raciti G, Vanella A, Stanzani S, Pellitteri R (2012) Expression of tissue transglutaminase on primary olfactory ensheathing cells cultures exposed to stress conditions. Neurosci Res 72:89–295. doi:10.1016/j.neures.2011.12.008

    Article  Google Scholar 

  8. Ramon-Cueto A, Avila J (1998) Olfactory ensheathing cells: properties and function. Brain Res Bull 46:175–187

    CAS  Article  PubMed  Google Scholar 

  9. Fairless R, Barnett SC (2005) Olfactory ensheathing cells: their role in central nervous system repair. Int J Biochem Cell Biol 37:693–699

    CAS  Article  PubMed  Google Scholar 

  10. Yang H, He BR, Hao DJ (2014) Biological roles of olfactory ensheathing cells in facilitating neural regeneration: a systematic review. Mol Neurobiol 51:168–179. doi:10.1007/s12035-014-8664-2

    Article  PubMed  Google Scholar 

  11. Mackay-Sim A, St John JA (2011) Olfactory ensheathing cells from the nose: clinical application in human spinal cord injuries. Exp Neurol 229:174–180

    Article  PubMed  Google Scholar 

  12. Woodhall E, West AK, Chuah MI (2001) Cultured olfactory ensheathing cells express nerve growth factor, brain-derived neurotrophic factor, glia cell line-derived neurotrophic factor and their receptors. Brain Res Mol Brain Res 88:203–213

    CAS  Article  PubMed  Google Scholar 

  13. Franssen EH, de Bree FM, Verhaagen J (2007) Olfactory ensheathing glia: their contribution to primary olfactory nervous system regeneration and their regenerative potential following transplantation into the injured spinal cord. Brain Res Rev 56:236–258

    Article  PubMed  Google Scholar 

  14. Pellitteri R, Spatuzza M, Stanzani S, Zaccheo D (2010) Biomarkers expression in rat olfactory ensheathing cells. Front Biosci 2:289–298

    Article  Google Scholar 

  15. Pellitteri R, Cova L, Zaccheo D, Silani V, Bossolasco P (2015) Phenotypic modulation and neuroprotective effects of olfactory ensheathing cells: a promising tool for cell therapy. Stem Cell Rev Rep. doi:10.1007/s12015-015-9635-3

    Google Scholar 

  16. Barnett SC, Riddell JS (2004) Olfactory ensheathing cells (OECs) and the treatment of CNS injury: advantages and possible caveats. J Anat 204:57–67

    Article  PubMed  PubMed Central  Google Scholar 

  17. Zhang J, Chen H, Duan Z, Chen K, Liu Z, Zhang L, Yao D, Li B (2016) The effects of Co transplantation of olfactory ensheathing cells and Schwann cells on local inflammation environment in the contused spinal cord of rats. Mol Neurobiol. doi:10.1007/s12035-016-9709-5

    Google Scholar 

  18. Raisman G, Carlstedt T, Choi D, Li Y (2011) Clinical prospects for transplantation of OECs in the repair of brachial and lumbosacral plexus injuries: opening a door. Exp Neurol 229:168–173

    Article  PubMed  Google Scholar 

  19. Chehrehasa F, Windus LC, Ekberg JA, Scott SE, Amaya D, Mackay-Sim A, St John JA (2010) Olfactory glia enhance neonatal axon regeneration. Mol Cell Neurosci 45:277–288. doi:10.1016/j.mcn.2010.07.002

    CAS  Article  PubMed  Google Scholar 

  20. Donnini S, Cantara S, Morbidelli L, Giachetti A, Ziche M (2006) FGF-2 overexpression opposes the beta amyloid toxic injuries to the vascular endothelium. Cell Death Differ 13:1088–1096

    CAS  Article  PubMed  Google Scholar 

  21. Revilla S, Ursulet S, Álvarez-López MJ, Castro-Freire M, Perpiñá U, García-Mesa Y, Bortolozzi A, Giménez-Llort L et al (2014) Lenti-GDNF gene therapy protects against Alzheimer’s disease-like neuropathology in 3xTg-AD mice and MC65 cells. CNS Neurosci Ther 20(11):961–972. doi:10.1111/cns.12312

    CAS  Article  PubMed  Google Scholar 

  22. Choi J, Malakowsky CA, Talent JM, Conrad CC, Carroll CA, Weintraub ST, Gracy RW (2003) Anti-apoptotic proteins are oxidized by Aβ25–35 in Alzheimer’s fibroblasts. Biochim Biophys Acta 1637:135–141

    CAS  Article  PubMed  Google Scholar 

  23. Attems J, Walker L, Jellinger KA (2014) Olfactory bulb involvement in neurodegenerative diseases. Acta Neuropathol 127(4):459–475

    CAS  Article  PubMed  Google Scholar 

  24. Pellitteri R, Spatuzza M, Russo A, Stanzani S (2007) Olfactory ensheathing cells exert a trophic effect on the hypothalamic neurons in vitro. Neurosci Lett 417:24–29

    CAS  Article  PubMed  Google Scholar 

  25. Chuah MI, Au C (1993) Cultures of ensheathing cells from neonatal rat olfactory bulbs. Brain Res 601:213–220

    CAS  Article  PubMed  Google Scholar 

  26. Pellitteri R, Spatuzza M, Russo A, Zaccheo D, Stanzani S (2009) Olfactory ensheathing cells represent an optimal substrate for hippocampal neurons: an in vitro study. Int J Dev Neurosci 27:453–458

    Article  PubMed  Google Scholar 

  27. Campisi A, Caccamo D, Raciti G, Cannavò G, Macaione V, Currò M, Macaione S, Vanella A et al (2003) Glutamate-induced increases in transglutaminase activity in primary cultures of astroglial cells. Brain Res 978:24–30

    CAS  Article  PubMed  Google Scholar 

  28. Campisi A, Caccamo D, Li Volti G, Currò M, Parisi G, Avola R, Vanella A, Ientile R (2004) Glutamate-evoked redox state alterations are involved in tissue transglutaminase upregulation in primary astrocyte cultures. FEBS Lett 578:80–84

    CAS  Article  PubMed  Google Scholar 

  29. Chen CJ, Liao SL, Kuo JS (2000) Gliotoxic action of glutamate on cultured astrocytes. J Neurochem 75:1557–1565

    CAS  Article  PubMed  Google Scholar 

  30. Pastrana E, Moreno-Flores MT, Avila J, Wandosell F, Minichiello L, Diaz-Nido J (2007) BDNF production by olfactory ensheathing cells contributes to axonal regenerationof cultured adult CNS neurons. Neurochem Int 50:491–498

    CAS  Article  PubMed  Google Scholar 

  31. Sasaki M, Lankford KL, Radtke C, Honmou O, Kocsis JD (2011) Remyelination after olfactory ensheathing cell transplantation into diverse demyelinating environments. Exp Neurol 229:88–98

    Article  PubMed  Google Scholar 

  32. Johnson GV, Cox TM, Lockhart JP, Zinnerman MD, Miller ML, Powers RE (1997) Transglutaminase activity is increased in Alzheimer’s disease brain. Brain Res 751:323–329

    CAS  Article  PubMed  Google Scholar 

  33. Wang DS, Dickson DW, Malter JS (2008) Tissue transglutaminase, protein cross-linking and Alzheimer’s disease: review and views. Int J Clin Exp Pathol 1:5–18

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Ientile R, Currò M, Caccamo D (2015) Transglutaminase 2 and neuroinflammation. Amino Acids 47:19–26

    CAS  Article  PubMed  Google Scholar 

  35. Piacentini M, Farrace MG, Piredda L, Matarrese P, Ciccosanti F, Falasca L, Rodolfo C, Giammarioli AM et al (2002) Transglutaminase overexpression sensitizes neuronal cell lines to apoptosis by increasing mitochondrial membrane potential and cellular oxidative stress. J Neurochem 81:1061–1072

    CAS  Article  PubMed  Google Scholar 

  36. Tucholski J, Roth KA, Johnson GV (2006) Tissue transglutaminase overexpression in the brain potentiates calcium-induced hippocampal damage. J Neurochem 97:582–594

    CAS  Article  PubMed  Google Scholar 

  37. Lesort M, Tucholski J, Miller ML, Johnson GV (2000) Tissue transglutaminase: a possible role in neurodegenerative diseases. Prog Neurobiol 61:439–463

    CAS  Article  PubMed  Google Scholar 

  38. Smith MA, Rottkamp CA, Nunomura A, Raina AK, Perr G (2000) Oxidative stress in Alzheimer’s disease. Biochim Biophys Acta 1502:139–144

    CAS  Article  PubMed  Google Scholar 

  39. Sheng B, Wang X, Su B, Lee HG, Casadesus G, Perry G, Zhu X (2012) Impaired mitochondrial biogenesis contributes to mitochondrial dysfunction in Alzheimer’s disease. J Neurochem 120:419–429. doi:10.1111/j.1471-4159.2011.07581

    CAS  Article  PubMed  Google Scholar 

  40. Pellitteri R, Catania MV, Bonaccorso CM, Ranno E, Dell’Albani P, Zaccheo D (2014) Viability of olfactory ensheathing cells after hypoxia and serum deprivation: implication for therapeutic transplantation. J Neurosc Research 92:1757–1766. doi:10.1002/jnr.23442

  41. Castaño EM, Maarouf CL, Wu T, Leal MC, Whiteside CM, Lue LF, Kokjohn TA, Sabbagh MN et al (2013) Alzheimer disease periventricular white matter lesions exhibit specific proteomic profile alterations. Neurochem Int 62:145–156. doi:10.1016/j.neuint.2012.12.001

    Article  PubMed  Google Scholar 

  42. Peluso JJ (2003) Basic fibroblast growth factor (bFGF) regulation of the plasma membrane calcium ATPase (PMCA) as part of an anti-apoptotic mechanism of action. Biochem Pharmacol 66(8):1363–1369

    CAS  Article  PubMed  Google Scholar 

  43. Piacentini M, D’Eletto M, Farrace MG, Rodolfo C, Del Nonno F, Ippolito G, Falasca L (2014) Characterization of distinct sub-cellular location of transglutaminase type II: changes in intracellular distribution in physiological and pathological states. Cell Tissue Res 358:793–805

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  44. Kuo TF, Tatsukawa H, Kojima S (2011) New insights into the functions and localization of nuclear transglutaminase 2. FEBS J 278(24):4756–4767

    CAS  Article  PubMed  Google Scholar 

  45. Vanella L, Raciti G, Barbagallo I, Bonfanti R, Abraham N, Campisi A (2015) Tissue transglutaminase expression during neural differentiation of human mesenchymal stem cells. CNS Neurol Disord Drug Targets 14(1):24–32

    CAS  Article  PubMed  Google Scholar 

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Correspondence to Agata Campisi.

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The authors declare that they have no conflicts of interest.

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Rosalia Pellitteri and Roberta Bonfanti contributed equally to this work

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Pellitteri, R., Bonfanti, R., Spatuzza, M. et al. Effect of Some Growth Factors on Tissue Transglutaminase Overexpression Induced by β-Amyloid in Olfactory Ensheathing Cells. Mol Neurobiol 54, 6785–6794 (2017). https://doi.org/10.1007/s12035-016-0152-4

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  • DOI: https://doi.org/10.1007/s12035-016-0152-4

Keywords

  • Olfactory ensheathing cells
  • Tissue transglutaminase
  • Beta-amyloid fragments
  • Stress conditions
  • Growth factors
  • Neurotoxicity