Antioxidant and detoxycative mechanisms in central nervous system

REVIEW ARTICLE

Antioxidant and detoxycative mechanisms in central nervous system

Marzena Gutowicz 1

1. Katedra Fizjologii Stosowanej i Klinicznej, Wydział Lekarski i Nauk o Zdrowiu, Uniwersytet Zielonogórski,

Published: 2020-02-19
DOI: 10.5604/01.3001.0013.8548
GICID: 01.3001.0013.8548
Available language versions: en pl
Issue: Postepy Hig Med Dosw 2020; 74 : 1-11

 

Abstract

Since the brain contains a large amount of polyunsaturated fatty acids, consumes up to 20% of oxygen used by the whole body and exhibits low antioxidants activity, it seems to be especially vulnerable to oxidative stress. The most important antioxidant enzymes are superoxide dismutase (SOD), which catalyze the dismutation of superoxide anion to hydrogen peroxide, catalase (CAT), which converts toxic hydrogen peroxide to water and oxygen, and glutathione peroxidase (Se-GSHPx), which reduces hydrogen peroxide and organic peroxides with glutathione as the cofactor. Among other detoxifying enzymes, the most significant is glutathione transferase (GST), which shows detoksyvarious catalytic activities allowing for removal of xenobiotics, reducing organic peroxides and oxidized cell components. One of the most important brain nonenzymatic antioxidants is reduced glutathione (GSH), which (individually or in cooperation with peroxidases) participates in the reduction of free radicals, repair of oxidative damage and the regeneration of other antioxidants, such as ascorbate or tocopherol. Glutathione as a cosubstrate of glutathione transferase scavenges toxic electrophilic compounds. Although the etiology of the major neurodegenerative diseases are unknown, numerous data suggest that reactive oxygen species play an important role. Even a small change in the level of antioxidants can leads to the many disorders in the CNS.

References

  • 1. Ahmad S., Thulasingam M., Palombo I., Daley D.O., Johnson K.A.,Morgenstern R., Haeggström J.Z., Rinaldo-Matthis A.: Trimeric microsomalglutathione transferase 2 displays one third of the sitesreactivity. Biochim. Biophys. Acta, 2015;1854: 1365–1371
    Google Scholar
  • 2. Armstrong R.N.: Structure, catalytic mechanism, and evolutionof the glutathione transferases. Chem. Res. Toxicol., 1997; 10: 2–18
    Google Scholar
  • 3. Ball S.: Chemia szarych komórek. Neurochemia i toksykologiaośrodkowego układu nerwowego. Medyk Sp. Zo.o., Warszawa 2003
    Google Scholar
  • 4. Barańczyk-Kuźma A., Barszczewska I., Audus K.L.: The effect ofexo-and endogenous compounds on the activity of glutathione-Stransferasefrom monkey brain. Acta Biochim. Pol., 1992; 39: 133–138
    Google Scholar
  • 5. Barańczyk-Kuźma A, Kuźma M, Gutowicz M, Kaźmierczak B, SawickiJ.:Glutathione S-transferase pi as a target for tricyclic antidepressantsin human brain. Acta Biochim. Pol., 2004; 51: 207–212
    Google Scholar
  • 6. Barber S.C., Shaw P.J.: Oxidative stress in ALS: Key role in motor neuroninjury and therapeutic target. Free Radical Biol. Med., 2010; 48: 629–641
    Google Scholar
  • 7. Bilska A., Kryczyk A., Włodek L.: Różne oblicza biologicznej roliglutationu. Postępy Hig. Med. Dośw. 2007; 61: 438–453
    Google Scholar
  • 8. Bredel M.: Anticancer drug resistance in primary human braintumors. Brain Res. Rev., 2001; 35: 161–204
    Google Scholar
  • 9. Chelikani P., Fita I., Loewen P.C.: Diversity of structures and propertiesamong catalases. Cell Mol. Life Sci., 2004; 61: 192–208
    Google Scholar
  • 10. Chiueh C.C., Rauhala P.: The redox pathway of S-nitrosoglutathione,glutathione and nitric oxide in cell to neuron communications.Free Radic. Res., 1999; 31: 641–650
    Google Scholar
  • 11. Covarrubias-Pinto A., Acuña A.I., Beltrán F.A., Torres-Díaz L.,Castro M.A.: Old things new view: Ascorbic acid protects the brainin neurodegenerative disorders. J. Mol. Sci., 2015; 16: 28194–28217
    Google Scholar
  • 12. Dasari S., Gonuguntla S., Ganjayi M.S., Bukke S., Sreenivasulu B.,Meriga B.: Genetic polymorphism of glutathione S-transferases: Relevanceto neurological disorders. Pathophysiology, 2018; 25: 285–292
    Google Scholar
  • 13. Dringen R.: Metabolism and functions of glutathione in brain.Prog. Neurobiol., 2000; 62: 649–671
    Google Scholar
  • 14. Dringen R., Brandmann M., Hohnholt M.C., Blumrich E.M.: Glutathione-dependent detoxification processes in astrocytes. Neurochem.Res., 2015; 40: 2570–2582
    Google Scholar
  • 15. Dröge W.: Free radicals in the physiological control of cell function.Physiol. Rev., 2002; 82: 47–95
    Google Scholar
  • 16. Emerit I., Filipe P., Freitas J., Fernandes A., Garban F., Vassy J.:Assaying binding capacity of Cu,ZnSOD and MnSOD: demonstrationof their localization in cells and tissues. Methods Enzymol.,2002; 349: 321–327
    Google Scholar
  • 17. Engin K.N.: Alpha-tocopherol: looking beyond an antioxidant.Mol. Vis., 2009; 15: 855–860
    Google Scholar
  • 18. Floriańczyk B., Kaczmarczyk R., Osuchowski J., Stryjecka-ZimmerM., Trojanowski T., Marzec Z.: Metallothioneins and microelementsin brain tumours. Ann. Univ. Mariae Curie Sklodowska,2003; 58: 1–4
    Google Scholar
  • 19. Flynn J.M, Melov S: SOD2 in mitochondrial dysfunction and neurodegeneration.Free Radical Biol. Med., 2013; 62: 4–12
    Google Scholar
  • 20. Frova C.: Glutathione transferases in the genomics era: new insightsand perspectives. Biomol. Eng., 2006; 23: 149–169
    Google Scholar
  • 21. Gallagher E.P., Gardner J.L., Barber D.S.: Several glutathione Stransferaseisozymes that protect against oxidative injury are expressedin human liver mitochondria. Biochem. Pharmacol., 2006;71: 1619–1628
    Google Scholar
  • 22. Gilgun-Sherki Y., Melamed E., Offen D.: Oxidative stress inducedneurodegenerative diseases: The need for antioxidants that penetratethe blood brain barrier. Neuropharmacology, 2001; 40: 959–975
    Google Scholar
  • 23. Gulick A.M., Fahl W.E.: Mammalian glutathione S-transferase:regulation of an enzyme system to achieve chemotherapeutic efficacy.Pharmacol. Ther. 1995; 66: 237–257
    Google Scholar
  • 24. Gutowicz M.: Wpływ reaktywnych form tlenu na ośrodkowyukład nerwowy. Postępy Hig. Med. Dośw., 2011; 65: 104–113
    Google Scholar
  • 25. Gutowicz M., Kaźmierczak B., Barańczyk-Kuźma A.: The influenceof heroin abuse on glutathione-dependent enzymes in humanbrain. Drug Alcohol Depend., 2011; 113: 8–12
    Google Scholar
  • 26. Gutowicz M., Sadurska B., Chołojczyk M., Pokorska-Lis M.,Siwińska-Ziółkowska A., Barańczyk-Kuźma A.: Antioxidant statusin different regions of heroin addicts’ brain. Environ. Toxicol. Pharmacol.,2006; 21: 80–85
    Google Scholar
  • 27. Haimeur A., Conseil G., Deeley R.G., Cole S.P.: The MRP-relatedand BCRP/ABCG2 multidrug resistance proteins: biology, substratespecificity and regulation. Curr. Drug Metab., 2004; 5: 21–53
    Google Scholar
  • 28. Hayes J.D., Flanagan J.U., Jowsey I.R.: Glutathione transferases.Annu. Rev. Pharmacol. Toxicol., 2005; 45: 51–88
    Google Scholar
  • 29. Hayes J.D., McLellan L.I.: Glutathione and glutathione-dependentenzymes represent a co-ordinately regulated defence against oxidativestress. Free Radic. Res., 1999; 31: 273–300
    Google Scholar
  • 30. Hayes J.D., Pulford D.J.: The glutathione S-transferase supergenefamily: regulation of GST and the contribution of the isoenzymesto cancer chemoprotection and drug resistance. Crit. Rev. Biochem.Mol. Biol., 1995; 30: 445–600
    Google Scholar
  • 31. Harrison F.E., Bowman G.L., Polidori M.C.: Ascorbic acid and thebrain: Rationale for the use against cognitive decline. Nutrients,2014; 6: 1752–1781
    Google Scholar
  • 32. Higasa S., Tsujimura M., Hiraoka M., Nakayama K., Yanagisawa Y.,Iwamoto S., Kagawa Y.: Polymorphism of glutathione S-transferaseP1 gene affects human vitamin C metabolism. Biochem. Biophys.Res. Commun., 2007; 364: 708–713
    Google Scholar
  • 33. Hirrlinger J., Schulz J.B., Dringen R.: Effects of dopamine on theglutathione metabolism of cultured astroglial cells: implications forParkinson’s disease. J. Neurochem., 2002; 82: 458–467
    Google Scholar
  • 34. Hurst R., Bao Y., Jemth P., Mannervik B., Williamson G.: Phospholipidhydroperoxide glutathione peroxidase activity of humanglutathione transferases. Biochem. J., 1998; 332: 97–100
    Google Scholar
  • 35. Ischiropoulos H., Beckman J.S.: Oxidative stress and nitrationin neurodegeneration: cause, effect, or association? J. Clin. Invest.,2003; 111: 163–169
    Google Scholar
  • 36. Janáky R., Ogita K., Pasqualotto B.A., Bains J.S., Oja S.S., YonedaY., Shaw C.A.: Glutathione and signal transduction in the mammalianCNS. J. Neurochem., 1999; 73: 889–902
    Google Scholar
  • 37. Jewett M., Dickson E., Brolin K., Negrini M., Jimenez-Ferrer I.,Swanberg M.: Glutathione S-transferase alpha 4 prevents dopamineneurodegeneration in a rat alpha-synuclein model of Parkinson’sdisease. Front. Neurol., 2018; 9: 222
    Google Scholar
  • 38. Johnson J.A., el Barbary A., Kornguth S.E., Brugge J.F., Siegel F.L.:Glutathione S-transferase isoenzymes in rat brain neurons and glia.J. Neurosci., 1993; 13: 2013–2023
    Google Scholar
  • 39. Kang Y., Viswanath V., Jha N., Qiao X., Mo J.Q., Andersen J.K.:Brain gamma-glutamyl cysteine synthetase (GCS) mRNA expressionpatterns correlate with regional-specific enzyme activities and glutathionelevels. J. Neurosci. Res., 1999; 58: 436–441
    Google Scholar
  • 40. Kargas C., Walter Z.: Znaczenie polimorfizmów genów transferazglutationowych człowieka. Postępy Bioch., 2003; 49: 85–95
    Google Scholar
  • 41. Kopczyńska E., Torliński L., Ziółkowski M.: Wpływ uzależnieniaod alkoholu na parametry stresu oksydacyjnego. Postępy Hig. Med.Dośw., 2001; 55: 95–111
    Google Scholar
  • 42. Krajka-Kuźniak V.: Indukcja enzymów II fazy jako strategia chemioprewencjinowotworów i innych schorzeń degeneracyjnych.Postępy Hig. Med. Dośw., 2007; 61: 627–638
    Google Scholar
  • 43. Kwak M.K., Wakabayashi N., Kensler T.W.: Chemopreventionthrough the Keap1-Nrf2 signaling pathway by phase 2 enzyme inducers.Mutat. Res., 2004; 555: 133–148
    Google Scholar
  • 44. Lee S.J., Koh J.Y.: Roles of zinc and metallothionein-3 in oxidativestress-induced lysosomal dysfunction, cell death, and autophagy inneurons and astrocytes. Mol. Brain, 2010; 3: 30
    Google Scholar
  • 45. Lei X.G., Cheng W.H., McClung J.P.: Metabolic regulation andfunction of glutathione peroxidase-1. Annu. Rev. Nutr., 2007; 27:41–61
    Google Scholar
  • 46. Lindenau J., Noack H., Possel H., Asayama K.: Cellular distributionof superoxide dismutases in the rat CNS. Glia, 2000; 29: 25–34
    Google Scholar
  • 47. Luo C., Yang Q., Liu Y., Zhou S., Jiang J., Reiter R.J., BhattacharyaP., Cui Y., Yang H., Ma H., Yao J., Lawler S.E., Zhang X., Fu J. i wsp.:The multiple protective roles and molecular mechanisms of melatoninand its precursor N-acetylserotonin in targeting brain injuryand liver damage and in maintaining bone health. Free Radic. Biol.Med., 2019; 130: 215–233
    Google Scholar
  • 48. Mazzetti A.P., Fiorile M.C., Primavera A., Lo Bello M.: Glutathionetransferases and neurodegenerative diseases. Neurochem. Int.,2015; 82: 10–18
    Google Scholar
  • 49. Mohn E.S., Kuchan M.J., Erdman J.W., Neuringer M., MatthanN.R., Chen C.O., Johnson E.J.: The subcellular distribution of alphatocopherolin the adult primate brain and its relationship with membranearachidonic acid and its oxidation products. Antioxidants,2017; 6: 97
    Google Scholar
  • 50. Montoliu, C.; Monfort, P.; Carrasco, J.; Palacios, O.; Capdevila, M.:Hidalgo, J.; Felipo, V.: Metallothionein-III prevents glutamate and nitricoxide neurotoxicity in primary cultures of cerebellar neurons.J. Neurochem., 2000; 75: 266–273
    Google Scholar
  • 51. Morel F., Aninat C.: The glutathione transferase kappa family.Drug. Metab. Rev., 2011; 43: 281–291
    Google Scholar
  • 52. Nakazawa T., Miyanoki Y., Urano Y., Uehara M., Saito Y., NoguchiN.: Effect of vitamin E on 24(S)-hydroxycholesterol-inducednecroptosis-like cell death and apoptosis. J. Steroid Biochem. Mol.Biol., 2017; 169: 69–76
    Google Scholar
  • 53. Nappi A.J., Vass E.: Iron, metalloenzymes and cytotoxic reactions.Cell Mol. Biol., 2000; 46: 637–647
    Google Scholar
  • 54. Nazıroğlu M.: Molecular role of catalase on oxidative stress-inducedCa2+ signaling and TRP cation channel activation in nervoussystem. J. Recept. Signal Transduct. Res., 2012; 32: 134–141
    Google Scholar
  • 55. Oakley A.J.: Glutathione transferases: new functions. Curr. Opin.Struct. Biol., 2005; 15: 716–723
    Google Scholar
  • 56. Ookawara T., Imazeki N., Matsubara O., Kizaki T., Oh-Ishi S.,Nakao C., Sato Y., Ohno H.: Tissue distribution of immunoreactivemouse extracellular superoxide dismutase. Am. J. Physiol., 1998;275: 840–847
    Google Scholar
  • 57. Pinarbasi H., Silig Y., Gurelik M.: Genetic polymorphisms of GSTsand their association with primary brain tumor incidence. CancerGenet. Cytogenet, 2005; 156: 144–149
    Google Scholar
  • 58. Popławski P.T., Derlacz R.A.: Jak działa melatonina? PostępyBioch. 2003; 49: 9–17
    Google Scholar
  • 59. Rahman Q., Abidi P., Afaq F., Schiffmann D., Mossman B.T., KampD.W., Athar M.: Glutathione redox system in oxidative lung injury.Crit. Rev. Toxicol., 1999; 29: 543–568
    Google Scholar
  • 60. Raps S.P., Lai J.C., Hertz L., Cooper A.J.: Glutathione is presentin high concentrations in cultured astrocytes but not in culturedneurons. Brain Res., 1989; 493: 398–401
    Google Scholar
  • 61. Ravindranath V.: Metabolism of xenobiotics in the central nervoussystem: implications and challenges. Biochem. Pharmacol.,1998; 56: 547–551
    Google Scholar
  • 62. Ruttkay-Nedecky B., Nejdl L., Gumulec J., Zitka O., Masarik M.,Eckschlager T., Adam V., Kizek R.: The role of metallothionein inoxidative stress. Int. J. Mol. Sci., 2013; 14: 6044–6066
    Google Scholar
  • 63. Rybnikova E., Damdimopoulos A.E., Gustafsson J.A., Spyrou G.,Pelto-Huikko M.: Expression of novel antioxidant thioredoxin-2 inthe rat brain. Eur. J. Neurosci., 2000; 12: 1669–1678
    Google Scholar
  • 64. Salinas A.E., Wong M.G.: Glutathione S-transferases – a review.Curr. Med. Chem., 1999; 6: 279–309
    Google Scholar
  • 65. Saydam N., Kirb A., Demir O., Hazan E., Oto O., Saydam O., GünerG.: Determination of glutathione, glutathione reductase, glutathioneperoxidase and glutathione S-transferase levels in human lungcancer tissues. Cancer Lett., 1997; 119: 13–19
    Google Scholar
  • 66. Sheehan D., Meade G., Foley V.M., Dowd C.A.: Structure, functionand evolution of glutathione transferases: implications for classificationof non-mammalian members of an ancient enzyme superfamily.Biochem. J., 2001; 360: 1–16
    Google Scholar
  • 67. Sheweita S.A.: Drug-metabolizing enzymes: mechanisms andfunctions. Curr. Drug Metab., 2000; 1: 107–132
    Google Scholar
  • 68. Sjögren T., Nord J., Ek M., Johansson P., Liu G., Geschwindner S.:Crystal structure of microsomal prostaglandin E2 synthase providesinsight into diversity in the MAPEG superfamily. Proc. Natl. Acad.Sci. USA, 2013; 110: 3806–3811
    Google Scholar
  • 69. Slemmer J.E., Shacka J.J., Sweeney M.I., Weber J.T.: Antioxidantsand free radical scavengers for the treatment of stroke, traumaticbrain injury and aging. Curr. Med. Chem., 2008; 15: 404–414
    Google Scholar
  • 70. Slivka A., Spina M.B., Cohen G.: Reduced and oxidized glutathionein human and monkey brain. Neurosci Lett., 1987; 74: 112–118
    Google Scholar
  • 71. Smeyne M., Smeyne R.J.: Glutathione metabolism and Parkinson’sdisease. Free Radic. Biol. Med., 2013; 62: 13–25
    Google Scholar
  • 72. Smirnoff N.: Ascorbic acid metabolism and functions: A comparisonof plants and mammals. Free Radic. Biol. Med., 2018; 122: 116–129
    Google Scholar
  • 73. Stahl W., Sies H.: Antioxidant defense: vitamins E and C and carotenoids.Diabetes, 1997; 46 (Suppl. 2): 14–18
    Google Scholar
  • 74. Strazielle N., Khuth S.T., Ghersi-Egea J.F.: Detoxification systems,passive and specific transport for drugs at the blood-CSF barrierin normal and pathological situations. Adv. Drug Deliv. Rev., 2004;56: 1717–1740
    Google Scholar
  • 75. Tan D.X., Manchester L.E., Reiter R.J., Qi W.B., Karbownik M.,Calvo M.: Significance of melatonine in antioxidative defence system:Reactions and products. Biol. Signals Recept., 2000; 9: 137–159
    Google Scholar
  • 76. Tetlow N., Robinson A., Mantle T., Board P.: Polymorphism ofhuman mu class glutathione transferases. Pharmacogenetics, 2004;14: 359–368
    Google Scholar
  • 77. Tuteja N., Tuteja R.: Unraveling DNA repair in human: molecularmechanisms and consequences of repair defect. Crit. Rev. Biochem.Mol. Biol., 2001; 36: 261–290
    Google Scholar
  • 78. Valko M., Leibfritz D., Moncol J., Cronin M.T., Mazur M., TelserJ.: Free radicals and antioxidants in normal physiological functionsand human disease. Int. J. Biochem. Cell Biol., 2007; 39: 44–84
    Google Scholar
  • 79. Zabłocka A., Janusz M.: Dwa oblicza wolnych rodników tlenowych.Postępy Hig. Med. Dośw., 2008; 62: 118–124
    Google Scholar
  • 80. Zasadowski A., Wysocki A. D., Barski D., Spodniewska A.: Someaspects of reactive oxygen species (ROS) and antioxidative systemagent`s action. Short Review. Acta Toxicol., 2004; 12: 5–19
    Google Scholar
  • 81. Zecca L., Tampellini D., Gatti A., Crippa R., Eisner M., Sulzer D.,Ito S., Fariello R., Gallorini M.: The neuromelanin of human substantianigra and its interaction with metals. J. Neural. Transm.,2002; 109: 663–672
    Google Scholar
  • 82. Zimatkin S.M., Lindros K.O.: Distribution of catalase in rat brain:aminergic neurons as possible targets for ethanol effects. Alcohol.Alcohol, 1996; 31: 167–174
    Google Scholar

Full text

Skip to content