The journal of nutrition, health & aging

, Volume 19, Issue 2, pp 198–205 | Cite as

Dual effect of docosahexaenoic acid (attenuation or amplification) on C22:0-, C24:0-, and C26:0-Induced mitochondrial dysfunctions and oxidative stress on human neuronal SK-N-BE cells

  • A. Zarrouk
  • T. Nury
  • J. M. Riedinger
  • O. Rouaud
  • M. Hammami
  • Gérard Lizard
Article

Abstract

Increased levels of C22:0, C24:0 and C26:0 were found in cortical lesions of patients with Alzheimer’s disease (AD). So, it was of interest to precise the cytotoxic effects of these fatty acids, and to determine whether docosahexaenoic acid (DHA), described to prevent AD, can attenuate their eventual side effects. Human neuronal SK-N-BE cells were cultured in the absence or presence of C22:0, C24:0 or C26:0 (0.1–20 μM) without or with DHA (50–150 μM). C22:0, C24:0 and C26:0 induce an inhibition of cell growth, a loss of Δψm, an overproduction of reactive oxygen species (ROS), a decrease of reduced glutathione, and a lipid peroxidation. DHA attenuates C22:0, C24:0 and C26:0 induced-mitochondrial dysfunctions and/or cell growth inhibition measured with MTT whatever the concentrations considered, whereas it can either decrease or amplify (especially at 150 μM) ROS overproduction. C22:0, C24:0 and C26:0 have neurotoxic activities, and depending on its concentration, DHA attenuates or not fatty acid-induced side effects.

Keywords

DHA fatty acids mitochondrial dysfunctions oxidative stress lipid peroxidation SK-N-BE cells 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Jack CR Jr, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, Petersen RC, Trojanowski JQ. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol. 2010;9, 119–128.CrossRefPubMedCentralPubMedGoogle Scholar
  2. 2.
    Zhou ZD, Chan CH, Ma QH, Xu XH, Xiao ZC, Tan EK. The roles of amyloid precursor protein (APP) in neurogenesis: Implications to pathogenesis and therapy of Alzheimer disease. Cell Adh Migr. 2011;5, 280–292.CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Kurz A, Perneczky R. Amyloid clearance as a treatment target against Alzheimer’s disease. J Alzheimers Dis. 2011;24 Suppl 2, 61–73.PubMedGoogle Scholar
  4. 4.
    Cavallucci V, D’Amelio M, Cecconi F. Aβ toxicity in Alzheimer’s disease. Mol Neurobiol. 2012;45, 366–378.CrossRefPubMedGoogle Scholar
  5. 5.
    Iqbal K, Liu F, Gong CX, Grundke-Iqbal I. Tau in Alzheimer disease and related tauopathies. Curr Alzheimer Res. 2010;7, 656–664.CrossRefPubMedCentralPubMedGoogle Scholar
  6. 6.
    Grimm MO, Rothhaar TL, Hartmann T. The role of APP proteolytic processing in lipid metabolism. Exp Brain Res. 2012;217, 365–375.CrossRefPubMedGoogle Scholar
  7. 7.
    Björkhem I, Cedazo-Minguez A, Leoni V, Meaney S. Oxysterols and neurodegenerative diseases. Mol. Aspects Med. 2009;30, 171–179.CrossRefPubMedGoogle Scholar
  8. 8.
    Iuliano L. Pathways of cholesterol oxidation via non-enzymatic mechanisms. Chem Phys Lipids. 2011;164, 457–468.CrossRefPubMedGoogle Scholar
  9. 9.
    Vaya J, Schipper HM. Oxysterols, cholesterol homeostasis, and Alzheimer disease. J Neurochem. 2007;102, 1727–1237.CrossRefPubMedGoogle Scholar
  10. 10.
    Liu CC, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol. 2013;9, 106–118.CrossRefPubMedCentralPubMedGoogle Scholar
  11. 11.
    Titorenko VI, Terlecky SR. Peroxisome metabolism and cellular aging. Traffic. 2011;12, 252–259.CrossRefPubMedCentralPubMedGoogle Scholar
  12. 12.
    Schrader M, Fahimi HD. The peroxisome: still a mysterious organelle. Histochem Cell Biol. 2008;129, 421–440.CrossRefPubMedCentralPubMedGoogle Scholar
  13. 13.
    Lizard G, Rouaud O, Demarquoy J, Cherkaoui-Malki M, Iuliano L. Potential roles of peroxisomes in Alzheimer’s disease and in dementia of the Alzheimer’s type. J Alzheimers Dis. 2012;29, 241–254.PubMedGoogle Scholar
  14. 14.
    Santos MJ, Quintanilla RA, Toro A, Grandy R, Dinamarca MC, Godoy JA, Inestrosa NC. Peroxisomal proliferation protects from beta-amyloid neurodegeneration. J Biol Chem. 2005;280, 41057–41068.CrossRefPubMedGoogle Scholar
  15. 15.
    Shi R, Zhang Y, Shi Y, Shi S, Jiang L. Inhibition of peroxisomal β-oxidation by thioridazine increases the amount of VLCFAs and Aβ generation in the rat brain. Neurosci Lett. 2012;528, 6–10.CrossRefPubMedGoogle Scholar
  16. 16.
    Cimini A, Moreno S, D’Amelio M, Cristiano L, D’Angelo B, Falone S, Benedetti E, Carrara P, Fanelli F, Cecconi F, Amicarelli F, Cerù MP. Early biochemical and morphological modifications in the brain of a transgenic mouse model of Alzheimer’s disease: a role for peroxisomes. J Alzheimers Dis. 2009;18, 935–952.PubMedGoogle Scholar
  17. 17.
    Fanelli F, Sepe S, D’Amelio M, Bernardi C, Cristiano L, Cimini A, Cecconi F, Ceru MP, Moreno S. Age-dependent roles of peroxisomes in the hippocampus of a transgenic mouse model of Alzheimer’s disease. Mol Neurodegener. 2013;8: 8. doi: 10.1186/1750-1326-8-8.CrossRefPubMedCentralPubMedGoogle Scholar
  18. 18.
    Kou J, Kovacs GG, Höftberger R, Kulik W, Brodde A, Forss-Petter S, Hönigschnabl S, Gleiss A, Brügger B, Wanders R, Just W, Budka H, Jungwirth S, Fischer P, Berger J. Peroxisomal alterations in Alzheimer’s disease. Acta Neuropathol. 2011;122, 271–283.CrossRefPubMedCentralPubMedGoogle Scholar
  19. 19.
    Cai Z, Zhao B, Ratka A. Oxidative stress and β-amyloid protein in Alzheimer’s disease. Neuromolecular Med. 2011;13, 223–250.CrossRefPubMedGoogle Scholar
  20. 20.
    Maruszak A, Zekanowski C. Mitochondrial dysfunction and Alzheimer’s disease. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35, 320–330.CrossRefPubMedGoogle Scholar
  21. 21.
    Baarine M, Ragot K, Athias A, Nury T, Kattan Z, Genin EC, Andreoletti P, Ménétrier F, Riedinger JM, Bardou M, Lizard G. Incidence of Abcd1 level on the induction of cell death and organelle dysfunctions triggered by very long chain fatty acids and TNF-a on oligodendrocytes and astrocytes. Neurotoxicology 2012;33, 212- 218.CrossRefPubMedGoogle Scholar
  22. 22.
    Baarine M, Andréoletti P, Athias A, Nury T, Zarrouk A, Ragot K, Vejux A, Riedinger JM, Kattan Z, Bessede G, Trompier D, Savary S, Cherkaoui-Malki M, Lizard G. Evidence of oxidative stress in very long chain fatty acid-treated oligodendrocytes and potentialization of ROS production using RNA interferencedirected knockdown of ABCD1 and ACOX1 peroxisomal proteins. Neuroscience 2012;213, 1–18.CrossRefPubMedGoogle Scholar
  23. 23.
    Zarrouk A, Vejux A, Nury T, El Hajj HI, Haddad M, Cherkaoui-Malki M, Riedinger JM, Hammami M, Lizard G. Induction of mitochondrial changes associated with oxidative stress on very long chain fatty acids (C22:0, C24:0, or C26:0)-treated human neuronal cells (SK-N-BE). Oxid Med Cell Longev. 2012;2012:623257. doi: 10.1155/2012/623257.CrossRefPubMedCentralPubMedGoogle Scholar
  24. 24.
    Lukiw WJ, Cui JG, Marcheselli VL, Bodker M, Botkjaer A, Gotlinger K, Serhan CN, Bazan NG. A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. J Clin Invest. 2005;115, 2774–2783.CrossRefPubMedCentralPubMedGoogle Scholar
  25. 25.
    Stark DT, Bazan NG. Neuroprotectin D1 induces neuronal survival and downregulation of amyloidogenic processing in Alzheimer’s disease cellular models. Mol Neurobiol. 2011;43, 131–138.CrossRefPubMedGoogle Scholar
  26. 26.
    Tanito M, Brush RS, Elliott MH, Wicker LD, Henry KR, Anderson RE. High levels of retinal membrane docosahexaenoic acid increase susceptibility to stress-induced degeneration. J Lipid Res. 2009;50, 807–819.CrossRefPubMedCentralPubMedGoogle Scholar
  27. 27.
    Muntané G, Janué A, Fernandez N, Odena MA, Oliveira E, Boluda S, Portero-Otin M, Naudí A, Boada J, Pamplona R, Ferrer I. Modification of brain lipids but not phenotype in alpha-synucleinopathy transgenic mice by long-term dietary n-3 fatty acids. Neurochem Int. 2010;56, 318–328.CrossRefPubMedGoogle Scholar
  28. 28.
    Takemoto Y, Suzuki Y, Horibe R, Shimozawa N, Wanders RJ, Kondo N. Gas chromatography/mass spectrometry analysis of very long chain fatty acids, docosahexaenoic acid, phytanic acid and plasmalogen for the screening of peroxisomal disorders. Brain Dev. 2003;25, 481–487.CrossRefPubMedGoogle Scholar
  29. 29.
    Bass DA, Parce JW, Dechatelet LR, Szejda P, Seeds MC, Thomas M. Flow cytometric studies of oxidative product formation by neutrophils: a graded response to membrane stimulation. J. Immunol. 1983;130, 1910–1917.PubMedGoogle Scholar
  30. 30.
    Rothe G, Valet G. Flow cytometric analysis of respiratory burst activity in phagocytes with hydroethidine and 2’,7’-dichlorofluorescin. J Leukoc Biol. 1990;47, 440–448.PubMedGoogle Scholar
  31. 31.
    Hedley DW, Chow S. Evaluation of methods for measuring cellular glutathione content using flow cytometry. Cytometry 1994;15, 349–358.CrossRefPubMedGoogle Scholar
  32. 32.
    Khatoon F, Moinuddin, Alam K, Ali A. Physicochemical and immunological studies on 4-hydroxynonenal modified HSA: implications of protein damage by lipid peroxidation products in the etiopathogenesis of SLE. Hum. Immunol. 2012;73, 1132–1139.CrossRefPubMedGoogle Scholar
  33. 33.
    Grimsrud PA, Xie H, Griffin TJ, Bernlohr DA. Oxidative stress and covalent modification of protein with bioactive aldehydes. J Biol Chem. 2008;283, 21837- 21841.CrossRefPubMedCentralPubMedGoogle Scholar
  34. 34.
    Pikuleva IA. Cholesterol-metabolizing cytochromes P450. Drug Metab Dispos. 2006;34, 513–520.CrossRefPubMedGoogle Scholar
  35. 35.
    Singh S, Kushwah AS, Singh R, Farswan M, Kaur R. Current therapeutic strategy in Alzheimer’s disease. Eur Rev Med Pharmacol Sci. 2012;16, 1651–1664.PubMedGoogle Scholar
  36. 36.
    Vejux A, Lizard G. Cytotoxic effects of oxysterols associated with human diseases: Induction of cell death (apoptosis and/or oncosis), oxidative and inflammatory activities, and phospholipidosis. Mol Aspects Med. 2009;30, 153–170.CrossRefPubMedGoogle Scholar
  37. 37.
    Dacks PA, Shineman DW, Fillit HM. Current evidence for the clinical use of longchain polyunsaturated n-3 fatty acids to prevent age-related cognitive decline and Alzheimer’s disease. J Nutr Health Aging. 2013;17, 240–251.CrossRefPubMedGoogle Scholar
  38. 38.
    Ouellet M, Emond V, Chen CT, Julien C, Bourasset F, Oddo S, LaFerla F, Bazinet RP, Calon F. Diffusion of docosahexaenoic and eicosapentaenoic acids through the blood-brain barrier: An in situ cerebral perfusion study. Neurochem Int. 2009;55, 476–482.CrossRefPubMedGoogle Scholar
  39. 39.
    Eckert GP, Lipka U, Muller WE. Omega-3 fatty acids in neurodegenerative diseases: focus on mitochondria. Prostaglandins Leukot Essent Fatty Acids. 2013;88, 105–114.CrossRefPubMedGoogle Scholar
  40. 40.
    Vandal M, Alata W, Tremblay C, Rioux-Perreault C, Salem Jr N, Calon F, Plourde M. Reduction in DHA transport to the brain of mice expressing human APOE4 compared to APOE2. J Neurochem. 2014;129:516–526.CrossRefPubMedGoogle Scholar

Copyright information

© Serdi and Springer-Verlag France 2014

Authors and Affiliations

  • A. Zarrouk
    • 1
    • 2
  • T. Nury
    • 1
  • J. M. Riedinger
    • 3
  • O. Rouaud
    • 4
  • M. Hammami
    • 2
  • Gérard Lizard
    • 1
    • 5
  1. 1.Equipe ‘Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique’ EA 7270 / Université de BourgogneINSERMDijonFrance
  2. 2.Faculté de Médecine, LR12ES05, Lab-NAFS ‘Nutrition - Functional Food & Vascular Health’Université de MonastirMonastirTunisia
  3. 3.Centre de Lutte Contre le Cancer GF Leclerc, Biologie MédicaleDijonFrance
  4. 4.Service de NeurologieCHU de DijonDijonFrance
  5. 5.Laboratoire BIO-peroxIL - EA 7270/INSERMFaculté des Sciences GabrielDijonFrance

Personalised recommendations