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Olfactory Ensheathing Cell-Conditioned Medium Reverts Aβ25–35-Induced Oxidative Damage in SH-SY5Y Cells by Modulating the Mitochondria-Mediated Apoptotic Pathway

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Abstract

Olfactory ensheathing cells (OECs) are a type of glia from the mammalian olfactory system, with neuroprotective and regenerative properties. β-Amyloid peptides are a major component of the senile plaques characteristic of the Alzheimer brain. The amyloid beta (Aβ) precursor protein is cleaved to amyloid peptides, and Aβ25–35 is regarded to be the functional domain of Aβ, responsible for its neurotoxic properties. It has been reported that Aβ25–35 triggers reactive oxygen species (ROS)-mediated oxidative damage, altering the structure and function of mitochondria, leading to the activation of the mitochondrial intrinsic apoptotic pathway. Our goal is to investigate the effects of OECs on the toxicity of aggregated Aβ25–35, in human neuroblastoma SH-SY5Y cells. For such purpose, SH-SY5Y cells were incubated with Aβ25–35 and OEC-conditioned medium (OECCM). OECCM promoted the cell viability and reduced the apoptosis, and decreased the intracellular ROS and the lipid peroxidation. In the presence of OECCM, mRNA and protein levels of antioxidant enzymes (SOD1 and SOD2) were upregulated. Concomitantly, OECCM decreased mRNA and the protein expression levels of cytochrome c, caspase-9, caspase-3, and Bax in SH-SY5Y cells, and increased mRNA and the protein expression level of Bcl-2. However, OECCM did not alter intracellular Ca2+ concentration in SH-SY5Y cells. Taken together, our data suggest that OECCM ameliorates Aβ25–35-induced oxidative damage in neuroblastoma SH-SY5Y cells by inhibiting the mitochondrial intrinsic pathway. These data provide new insights into the functional actions of OECCM on oxidative stress-induced cell damage.

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References

  • Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E (2011) Alzheimer’s disease. Lancet 377(9770):1019–1031. doi:10.1016/s0140-6736(10)61349-9

    Article  PubMed  Google Scholar 

  • Barnett SC, Chang L (2004) Olfactory ensheathing cells and CNS repair: going solo or in need of a friend? Trends Neurosci 27(1):54–60. doi:10.1016/j.tins.2003.10.011

    Article  CAS  PubMed  Google Scholar 

  • Blennow K, de Leon MJ, Zetterberg H (2006) Alzheimer’s disease. Lancet 368(9533):387–403. doi:10.1016/s0140-6736(06)69113-7

    Article  CAS  PubMed  Google Scholar 

  • Butterfield DA, Swomley AM, Sultana R (2013) Amyloid beta-peptide (1-42)-induced oxidative stress in Alzheimer disease: importance in disease pathogenesis and progression. Antioxid Redox Signal 19(8):823–835. doi:10.1089/ars.2012.5027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carvalho LA, Vitorino LC, Guimaraes RP, Allodi S, de Melo Reis RA, Cavalcante LA (2014) Selective stimulatory action of olfactory ensheathing glia-conditioned medium on oligodendroglial differentiation, with additional reference to signaling mechanisms. Biochem Biophys Res Commun 449(3):338–343. doi:10.1016/j.bbrc.2014.05.051

    Article  CAS  PubMed  Google Scholar 

  • Doraiswamy PM (2002) Non-cholinergic strategies for treating and preventing Alzheimer’s disease. CNS Drugs 16(12):811–824

    Article  CAS  PubMed  Google Scholar 

  • Doucette JR, Kiernan JA, Flumerfelt BA (1983) The re-innervation of olfactory glomeruli following transection of primary olfactory axons in the central or peripheral nervous system. J Anat 137(Pt 1):1–19

    PubMed  PubMed Central  Google Scholar 

  • Eftekharzadeh M, Nobakht M, Alizadeh A, Soleimani M, Hajghasem M, Kordestani Shargh B, Karkuki Osguei N, Behnam B, Samadikuchaksaraei A (2015) The effect of intrathecal delivery of bone marrow stromal cells on hippocampal neurons in rat model of Alzheimer’s disease. Iran J Basic Med Sci 18(5):520–525

    PubMed  PubMed Central  Google Scholar 

  • Ekberg JA, St John JA (2014) Crucial roles for olfactory ensheathing cells and olfactory mucosal cells in the repair of damaged neural tracts. Anat Rec 297(1):121–128. doi:10.1002/ar.22803

    Article  Google Scholar 

  • Fan CD, Li Y, Fu XT, Wu QJ, Hou YJ, Yang MF, Sun JY, Fu XY, Zheng ZC, Sun BL (2016) Reversal of beta-amyloid-induced neurotoxicity in PC12 cells by curcumin, the important role of ROS-mediated signaling and ERK pathway. Cell Mol Neurobiol. doi:10.1007/s10571-016-0362-3

    Google Scholar 

  • Garcia-Escudero V, Gargini R, Gallego-Hernandez MT, Garcia-Gomez A, Martin-Bermejo MJ, Simon D, Delicado A, Moreno-Flores MT, Avila J, Lim F (2011) A neuroregenerative human ensheathing glia cell line with conditional rapid growth. Cell Transplant 20(2):153–166. doi:10.3727/096368910x522108

    Article  PubMed  Google Scholar 

  • Gonzalez-Zulueta M, Ensz LM, Mukhina G, Lebovitz RM, Zwacka RM, Engelhardt JF, Oberley LW, Dawson VL, Dawson TM (1998) Manganese superoxide dismutase protects nNOS neurons from NMDA and nitric oxide-mediated neurotoxicity. J Neurosci 18(6):2040–2055

    CAS  PubMed  Google Scholar 

  • Hughes E, Burke RM, Doig AJ (2000) Inhibition of toxicity in the beta-amyloid peptide fragment beta-(25-35) using N-methylated derivatives: a general strategy to prevent amyloid formation. J Biol Chem 275(33):25109–25115. doi:10.1074/jbc.M003554200

    Article  CAS  PubMed  Google Scholar 

  • Jamasbi E, Wade JD, Separovic F, Hossain MA (2016) Amyloid beta (Abeta) peptide and factors that play important roles in Alzheimer’s disease. Curr Med Chem 23(9):884–892

    Article  CAS  PubMed  Google Scholar 

  • Jinbo L, Zhiyuan L, Zhijian Z, WenGe D (2013) Olfactory ensheathing cell-conditioned medium protects astrocytes exposed to hydrogen peroxide stress. Cell Mol Neurobiol 33(5):699–705. doi:10.1007/s10571-013-9937-4

    Article  PubMed  Google Scholar 

  • Jung Choi S, Kim MJ, Jin Heo H, Kim JK, Jin Jun W, Kim HK, Kim EK, Ok Kim M, Yon Cho H, Hwang HJ, Jun Kim Y, Shin DH (2009) Ameliorative effect of 1,2-benzenedicarboxylic acid dinonyl ester against amyloid beta peptide-induced neurotoxicity. Amyloid 16(1):15–24. doi:10.1080/13506120802676997

    Article  PubMed  Google Scholar 

  • Kim TD, Ryu HJ, Cho HI, Yang CH, Kim J (2000) Thermal behavior of proteins: heat-resistant proteins and their heat-induced secondary structural changes. Biochemistry 39(48):14839–14846

    Article  CAS  PubMed  Google Scholar 

  • Lee JK, Jin HK, Bae JS (2009) Bone marrow-derived mesenchymal stem cells reduce brain amyloid-beta deposition and accelerate the activation of microglia in an acutely induced Alzheimer’s disease mouse model. Neurosci Lett 450(2):136–141. doi:10.1016/j.neulet.2008.11.059

    Article  CAS  PubMed  Google Scholar 

  • Lee HJ, Lee JK, Lee H, Carter JE, Chang JW, Oh W, Yang YS, Suh JG, Lee BH, Jin HK, Bae JS (2012) Human umbilical cord blood-derived mesenchymal stem cells improve neuropathology and cognitive impairment in an Alzheimer’s disease mouse model through modulation of neuroinflammation. Neurobiol Aging 33(3):588–602. doi:10.1016/j.neurobiolaging.2010.03.024

    Article  CAS  PubMed  Google Scholar 

  • Lee IS, Jung K, Kim IS, Lee H, Kim M, Yun S, Hwang K, Shin JE, Park KI (2015) Human neural stem cells alleviate Alzheimer-like pathology in a mouse model. Mol Neurodegener 10:38. doi:10.1186/s13024-015-0035-6

    Article  PubMed  PubMed Central  Google Scholar 

  • Li Y, Field PM, Raisman G (1997) Repair of adult rat corticospinal tract by transplants of olfactory ensheathing cells. Science 277(5334):2000–2002

    Article  CAS  PubMed  Google Scholar 

  • Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443(7113):787–795. doi:10.1038/nature05292

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Qiu J, Xiong Y, Liu Z, Gao J (2013) The mitochondrial protective mechanism of olfactory ensheathing cells conditioned medium protects against H2O2-induced injury in astrocytes. Neurosci Lett 555:91–96. doi:10.1016/j.neulet.2013.09.011

    Article  CAS  PubMed  Google Scholar 

  • Marcus DL, Thomas C, Rodriguez C, Simberkoff K, Tsai JS, Strafaci JA, Freedman ML (1998) Increased peroxidation and reduced antioxidant enzyme activity in Alzheimer’s disease. Exp Neurol 150(1):40–44. doi:10.1006/exnr.1997.6750

    Article  CAS  PubMed  Google Scholar 

  • Mattson MP, Begley JG, Mark RJ, Furukawa K (1997) Abeta25-35 induces rapid lysis of red blood cells: contrast with Abeta1-42 and examination of underlying mechanisms. Brain Res 771(1):147–153

    Article  CAS  PubMed  Google Scholar 

  • Moreira PI, Carvalho C, Zhu X, Smith MA, Perry G (2010) Mitochondrial dysfunction is a trigger of Alzheimer’s disease pathophysiology. Biochim Biophys Acta 1802(1):2–10. doi:10.1016/j.bbadis.2009.10.006

    Article  CAS  PubMed  Google Scholar 

  • Moreno-Flores MT, Avila J (2006) The quest to repair the damaged spinal cord. Recent Pat CNS Drug Discov 1(1):55–63

    Article  CAS  PubMed  Google Scholar 

  • Moreno-Flores MT, Diaz-Nido J, Wandosell F, Avila J (2002) Olfactory ensheathing glia: drivers of axonal regeneration in the central nervous system? J Biomed Biotechnol 2(1):37–43. doi:10.1155/s1110724302000372

    Article  CAS  PubMed  Google Scholar 

  • Moreno-Flores MT, Lim F, Martin-Bermejo MJ, Diaz-Nido J, Avila J, Wandosell F (2003a) High level of amyloid precursor protein expression in neurite-promoting olfactory ensheathing glia (OEG) and OEG-derived cell lines. J Neurosci Res 71(6):871–881. doi:10.1002/jnr.10527

    Article  CAS  PubMed  Google Scholar 

  • Moreno-Flores MT, Lim F, Martin-Bermejo MJ, Diaz-Nido J, Avila J, Wandosell F (2003b) Immortalized olfactory ensheathing glia promote axonal regeneration of rat retinal ganglion neurons. J Neurochem 85(4):861–871

    Article  CAS  PubMed  Google Scholar 

  • Moreno-Flores MT, Bradbury EJ, Martin-Bermejo MJ, Agudo M, Lim F, Pastrana E, Avila J, Diaz-Nido J, McMahon SB, Wandosell F (2006) A clonal cell line from immortalized olfactory ensheathing glia promotes functional recovery in the injured spinal cord. Mol Ther 13(3):598–608. doi:10.1016/j.ymthe.2005.11.014

    Article  CAS  PubMed  Google Scholar 

  • Nafar F, Williams JB, Mearow KM (2015) Astrocytes release HspB1 in response to amyloid-β exposure in vitro. J Alzheimers Dis 49(1):251–263. doi:10.3233/JAD-150317

    Article  CAS  Google Scholar 

  • Nedelec S, Dubacq C, Trembleau A (2005) Morphological and molecular features of the mammalian olfactory sensory neuron axons: what makes these axons so special? J Neurocytol 34(1–2):49–64. doi:10.1007/s11068-005-5047-7

    Article  PubMed  Google Scholar 

  • Oliveira AA Jr, Hodges HM (2005) Alzheimer’s disease and neural transplantation as prospective cell therapy. Curr Alzheimer Res 2(1):79–95

    Article  CAS  PubMed  Google Scholar 

  • Pastrana E, Moreno-Flores MT, Gurzov EN, Avila J, Wandosell F, Diaz-Nido J (2006) Genes associated with adult axon regeneration promoted by olfactory ensheathing cells: a new role for matrix metalloproteinase 2. J Neurosci 26(20):5347–5359. doi:10.1523/jneurosci.1111-06.2006

    Article  CAS  PubMed  Google Scholar 

  • Pastrana E, Moreno-Flores MT, Avila J, Wandosell F, Minichiello L, Diaz-Nido J (2007) BDNF production by olfactory ensheathing cells contributes to axonal regeneration of cultured adult CNS neurons. Neurochem Int 50(3):491–498. doi:10.1016/j.neuint.2006.10.004

    Article  CAS  PubMed  Google Scholar 

  • 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(5):453–458. doi:10.1016/j.ijdevneu.2009.05.001

    Article  PubMed  Google Scholar 

  • Ramon-Cueto A, Plant GW, Avila J, Bunge MB (1998) Long-distance axonal regeneration in the transected adult rat spinal cord is promoted by olfactory ensheathing glia transplants. J Neurosci 18(10):3803–3815

    CAS  PubMed  Google Scholar 

  • Ramon-Cueto A, Cordero MI, Santos-Benito FF, Avila J (2000) Functional recovery of paraplegic rats and motor axon regeneration in their spinal cords by olfactory ensheathing glia. Neuron 25(2):425–435

    Article  CAS  PubMed  Google Scholar 

  • Reginensi D, Carulla P, Nocentini S, Seira O, Serra-Picamal X, Torres-Espin A, Matamoros-Angles A, Gavin R, Moreno-Flores MT, Wandosell F, Samitier J, Trepat X, Navarro X, del Rio JA (2015) Increased migration of olfactory ensheathing cells secreting the Nogo receptor ectodomain over inhibitory substrates and lesioned spinal cord. Cell Mol Life Sci 72(14):2719–2737. doi:10.1007/s00018-015-1869-3

    Article  CAS  PubMed  Google Scholar 

  • Roet KC, Verhaagen J (2014) Understanding the neural repair-promoting properties of olfactory ensheathing cells. Exp Neurol 261:594–609. doi:10.1016/j.expneurol.2014.05.007

    Article  CAS  PubMed  Google Scholar 

  • Roher AE, Esh CL, Kokjohn TA, Castano EM, Van Vickle GD, Kalback WM, Patton RL, Luehrs DC, Daugs ID, Kuo YM, Emmerling MR, Soares H, Quinn JF, Kaye J, Connor DJ, Silverberg NB, Adler CH, Seward JD, Beach TG, Sabbagh MN (2009) Amyloid beta peptides in human plasma and tissues and their significance for Alzheimer’s disease. Alzheimer’s Dement 5(1):18–29. doi:10.1016/j.jalz.2008.10.004

    Article  CAS  Google Scholar 

  • Scheff SW, Ansari MA, Mufson EJ (2016) Oxidative stress and hippocampal synaptic protein levels in elderly cognitively intact individuals with Alzheimer’s disease pathology. Neurobiol Aging 42:1–12. doi:10.1016/j.neurobiolaging.2016.02.030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shukla A, Mohapatra TM, Parmar D, Seth K (2014) Neuroprotective potentials of neurotrophin rich olfactory ensheathing cell’s conditioned media against 6OHDA-induced oxidative damage. Free Radic Res 48(5):560–571. doi:10.3109/10715762.2014.894636

    Article  CAS  PubMed  Google Scholar 

  • Soriano ME, Scorrano L (2011) Traveling bax and forth from mitochondria to control apoptosis. Cell 145(1):15–17. doi:10.1016/j.cell.2011.03.025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sugaya K, Alvarez A, Marutle A, Kwak YD, Choumkina E (2006) Stem cell strategies for Alzheimer’s disease therapy. Panminerva Med 48(2):87–96

    CAS  PubMed  Google Scholar 

  • Sun X, Chen WD, Wang YD (2015) Beta-Amyloid: the key peptide in the pathogenesis of Alzheimer’s disease. Front Pharmacol 6:221. doi:10.3389/fphar.2015.00221

    PubMed  PubMed Central  Google Scholar 

  • Tsunekawa H, Noda Y, Mouri A, Yoneda F, Nabeshima T (2008) Synergistic effects of selegiline and donepezil on cognitive impairment induced by amyloid beta (25-35). Behav Brain Res 190(2):224–232. doi:10.1016/j.bbr.2008.03.002

    Article  CAS  PubMed  Google Scholar 

  • 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. Mol Brain Res 88(1–2):203–213

    Article  CAS  PubMed  Google Scholar 

  • Wu QY, Li J, Feng ZT, Wang TH (2007) Bone marrow stromal cells of transgenic mice can improve the cognitive ability of an Alzheimer’s disease rat model. Neurosci Lett 417(3):281–285. doi:10.1016/j.neulet.2007.02.092

    Article  CAS  PubMed  Google Scholar 

  • Yang R, Wei L, Fu QQ, You H, Yu HR (2016) SOD3 ameliorates Abeta25-35-induced oxidative damage in SH-SY5Y cells by Inhibiting the mitochondrial pathway. Cell Mol Neurobiol. doi:10.1007/s10571-016-0390-z

    PubMed Central  Google Scholar 

  • Yu H, Yao L, Zhou H, Qu S, Zeng X, Zhou D, Zhou Y, Li X, Liu Z (2014) Neuroprotection against Abeta25-35-induced apoptosis by Salvia miltiorrhiza extract in SH-SY5Y cells. Neurochem Int 75:89–95. doi:10.1016/j.neuint.2014.06.001

    Article  CAS  PubMed  Google Scholar 

  • Yue W, Li Y, Zhang T, Jiang M, Qian Y, Zhang M, Sheng N, Feng S, Tang K, Yu X, Shu Y, Yue C, Jing N (2015) ESC-derived basal forebrain cholinergic neurons ameliorate the cognitive symptoms associated with Alzheimer’s disease in mouse models. Stem Cell Rep 5(5):776–790. doi:10.1016/j.stemcr.2015.09.010

    Article  CAS  Google Scholar 

  • Zeng Y, Rong M, Liu Y, Liu J, Lu M, Tao X, Li Z, Chen X, Yang K, Li C, Liu Z (2013) Electrophysiological characterisation of human umbilical cord blood-derived mesenchymal stem cells induced by olfactory ensheathing cell-conditioned medium. Neurochem Res 38(12):2483–2489. doi:10.1007/s11064-013-1186-x

    Article  CAS  PubMed  Google Scholar 

  • Zhang Q, Wu HH, Wang Y, Gu GJ, Zhang W, Xia R (2015) Neural stem cell transplantation decreases neuroinflammation in a transgenic mouse model of Alzheimer’s disease. J Neurochem. doi:10.1111/jnc.13413

    Google Scholar 

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Funding

This work was supported by grants from the National Natural Science Foundation of China (81670180, 81370077 and 81001220), the cutting-edge research project of the Chongqing Science and Technology Committee (CSTC2014JCYJA10014), the Scientific and Technological Research Programme of Chongqing Municipal Education Commission (KJ130320), NIG Collaborative Research Program (2016-A2-4), the Chongqing Science and Technology Committee (CSTC2016JCYJA0083), Beijing Municipal Science and Technology Commission, and Chongqing Municipal Commission of Health and Family Planning (2016MSXM103). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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    1. Research Center of Neuroscience, Chongqing Medical University, Chongqing, 400016, China

      Qing-Qing Fu, Jian-Zhang Cheng & Hua-Rong Yu

    2. Key Laboratory of Birth Defects and Reproductive Health of the National Health and Family Planning Commission, Chongqing Population and Family Planning Science and Technology Research Institute, Chongqing, 400020, China

      Li Wei

    3. Faculty of Experimental Sciences, Universidad Francisco de Vitoria, Pozuelo de Alarcón, 28223, Madrid, Spain

      Javier Sierra

    4. Department of Anatomy, Histology and Neuroscience, Faculty of Medicine, Universidad Autónoma de Madrid, 28029, Madrid, Spain

      María Teresa Moreno-Flores

    5. Affiliated Hospital of the Academy of Military Medical Sciences, Beijing, 100071, China

      Hua You

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    Qing-Qing Fu and Li Wei have contributed equally to this work.

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    Fu, QQ., Wei, L., Sierra, J. et al. Olfactory Ensheathing Cell-Conditioned Medium Reverts Aβ25–35-Induced Oxidative Damage in SH-SY5Y Cells by Modulating the Mitochondria-Mediated Apoptotic Pathway. Cell Mol Neurobiol 37, 1043–1054 (2017). https://doi.org/10.1007/s10571-016-0437-1

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