Skip to main content
Log in

Effects of L-mono Methyl-arginine, N-Acetyl-cysteine and Diphenyleniodonium on Free Radical Release in C6 Glial Cells Enriched in Hexacosenoic Acid

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Previously, we have shown that C6 glial cells enriched in hexacosenoic acid (HA) incubated with oxidative stressors released higher amounts of nitric oxide (NO) products and superoxide (O2), compared to native C6 cells. In the present study, we examined the effects of pre-treatment with some of free radical release inhibitors. The aim was to determine the origin of the enhanced generation of NO and superoxide, and to test the possibility of preventing it. Pre-treatment with L-mono-methyl-arginine and N-acetyl-cysteine in oxidized low-density lipoprotein (ox-LDL) exposed HA cells, inhibited not only nitrite but also superoxide production suggesting that (O2) anion could partially derive from inducible NO synthase. We also observed that ox-LDL treatment of HA cells reduced the intracellular glutathione levels and activated extracellular signal-related kinases. Since this signalling is related to neurotoxic effect, our data substantiate the role of the free radicals in X-linked adrenoleukodystrophy pathogenesis, as HA cells have been used as an in vitro model for this disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. R. P. Patel J. McAndrew H. Sellak C. R. White H. Jo B. A. Freeman V. M. Darley-Usmar (1999) ArticleTitleBiological aspects of reactive nitrogen species. Biochim. Biophys. Acta 1411 385–400

    Google Scholar 

  2. K. J. Smith R. Fapoor P. A. Felts (1999) ArticleTitleDemyelination: The role of reactive oxygen and nitrogen species. Brain Pathol 9 69–92 Occurrence Handle1:CAS:528:DyaK1MXht1CmsLc%3D Occurrence Handle9989453

    CAS  PubMed  Google Scholar 

  3. A. G. Gilg A. K. Singh I. Singh (2000) ArticleTitleInducible nitric oxide synthase in the central nervous system of patients with X-adrenoleukodystrophy. J. Neurophatol. Exp. Neurol 59 1063–1069

    Google Scholar 

  4. A. Di Biase S. Salvati L. Attorri D. Pietraforte (2002) ArticleTitleConsideration on X-Linked adrenoleuko dystrophy phatogenesis. Recent Res. Dev. Neurochem 5 49–56

    Google Scholar 

  5. H. W. Moser (1997) ArticleTitleAdrenoleukodystrophy: Phenotype, genetics pathogenesis and therapy. Brain 120 1486–1508

    Google Scholar 

  6. A. Di Biase R. Di Benedetto C. Fiorentini S. Travaglione S. Salvati L. Attorri D. Pietraforte (2004) ArticleTitleFree radical release in C6 glial cells enriched in hexacosenoic acid: Implication for X-linked adrenoleukodystrophy pathogenesis. Neurochem. Int 44 215–221

    Google Scholar 

  7. N. R. Bhat P. Zhang A. N. Bhat (1999) ArticleTitleCytokine induction of inducible nitric oxide synthase in an oligodendrocyte cell line: Role of p38 mitogen activated protein kinase activation. J. Neurochem 72 472–478

    Google Scholar 

  8. M. Mori T. Gotoh (2000) ArticleTitleRegulation of nitric oxide production by arginine metabolic enzymes. Biochem. Biophys. Res. Comm 274 715–719

    Google Scholar 

  9. J. T. Curnutte J. A. Badwey J. M. Robinson M. J. Karnovsky M. L. Karnowsky (1984) ArticleTitleStudies on the mechanism of superoxide release from human neutrophils stimulated with arachidonate. J. Biol. Chem 259 11851–11857

    Google Scholar 

  10. J. S. Beckman W. H. Koppenol (1996) ArticleTitleNitric oxide, superoxide and peroxinitrite: The good, the bad and ugly. Am. J. Physiol 271 C1424–C1437

    Google Scholar 

  11. V. O’Donnell D. G. Tew O. T. G. Jones P. J. England (1993) ArticleTitleStudies on the inhibitory mechanism of iodonium compounds with special reference to neutrophil NADPH oxidase. Biochem. J 290 41–49

    Google Scholar 

  12. W. Q. Li F. Dehnade M. Zafarullah (2000) ArticleTitleThiol antioxidant N-acethylcysteine activates extracellular signal regulated kinase signaling pathway in articular chondrocytes. Biochem. Biophys. Res. Comm 275 789–794

    Google Scholar 

  13. A. Huang C. Li R. L. Kao W. L. Stone (1999) ArticleTitleLipid hydroperoxides inhibit nitric oxide production in RAW264.7 macrophages. Free Radic. Biol. Med 26 526–537

    Google Scholar 

  14. D. L. Feinstein E. Galea S. Roberts H. Berquits H. Wang D. J. Reis (1994) ArticleTitleInduction of nitric oxide synthase in rat C6 glioma cells. J. Neurochem 62 315–321

    Google Scholar 

  15. K. Pahan G. Sheikh A. M. S. Namboodiri I. Singh (1998) ArticleTitleN-acetyl cysteine inhibits induction of NO production by endotoxin or cytokine stimulated rat peritoneal macrophages C6 glial cells and astrocytes. Free Radic. Biol. Med 24 39–48

    Google Scholar 

  16. E. Mazzi A. Becker F. A. Soliman (2003) ArticleTitleInflammation and inducible nitric oxide synthase have no effect on monoamine oxidase activity in glioma cells. Biochem. Pharmacol 65 1719–1727

    Google Scholar 

  17. M. Zafarullah W. Q. Sylvester J. Li M. Ahmad (2003) ArticleTitleMolecular mechanisms of N-acetylcysteine actions. Cell. Mol. Life Sci 60 6–20

    Google Scholar 

  18. P. Failli L. Palmier C. D’Alfonso L. Giovannelli S. Generini A. Del Rosso A. Pignone N. Stanflin S. Orsi L. Ziletti M. Catucci-Cerinic (2002) ArticleTitleEffect of N-acetyl-L-cysteine on peroxynitrite and superoxide anion production of lung alveor macrophages in systemic sclerosis. Nitric oxide 7 277–282

    Google Scholar 

  19. B. Mayer (2000) ArticleTitleNitric oxide synthases catalyze superoxide formation. FEBS Lett 24110 1–1

    Google Scholar 

  20. D. Stuehr S. Pou G.M. Rosen (2001) ArticleTitleOxygen reduction by nitric-oxide synthases. J. Biol. Chem 276 14533–14536

    Google Scholar 

  21. B. Fischer A. Knethen Particlevon B. Brune (2002) ArticleTitleDualism of oxidized lipoproteins in provoking and attenuating the oxidative burst in macrophages: Role of peroxisome proliferator-activated receptor γ. J. Immunol 168 2828–2834

    Google Scholar 

  22. J. N. Keller K. B. Hanni W. R. Markesbery (1999) ArticleTitleOxidized low-density lipoprotein induces neuronal death: Implications for calcium, reactive oxygen species and caspases. J. Neurochem 72 2601–2609

    Google Scholar 

  23. A. Heinloth K. Heermeier U. Raff C. Wanner J. Galle (2000) ArticleTitleStimulation of NADPH oxidase by oxidised low-density lipoprotein induces proliferation of human vascular endothelial cells. J. Am. Soc. Nephrol 10 1819–1825

    Google Scholar 

  24. S. Peuchen J. P. Bolanos S. J. R. Heales A. Almeida M. R. Duchen J. B. Clark (1997) ArticleTitleInterrelationships between astrocyte function, oxidative stress and antioxidant status within the central nervous system. Progr. Neurobiol 52 261–281

    Google Scholar 

  25. S. Cho M. Hazama Y. Urata S. Goto S. Horiuchi K. Sumikawa T. Kondo (1999) ArticleTitleProtective role of glutathione synthesis in response to oxidized low density lipoprotein in human vascular endothelial cells. Free Radic. Biol. Med 26 589–602

    Google Scholar 

  26. F. Bea F. N. Hudson A. Chait T. J. Kavanagh M. E. Rosenfeld (2003) ArticleTitleInduction of glutathione synthesis in macrophages by oxidized low-density lipoproteins is mediated by consensus antioxidant response elements. Circ. Res 92 386–93

    Google Scholar 

  27. M. Stanciu Y. Wang R. Kentor N. Burke S. Watkins G. Kress I. Reynolds E. Klann M. R. Angiolieri J. W. Johnson D. B. De Franco (2000) ArticleTitlePersistent activation of ERK contributes to glutamate-induced oxidative toxicity in a neuronal cell line and primary cortical neuron cultures. J. Biol. Chem 275 12200–12206

    Google Scholar 

  28. M. Marangolo M. McGee K. F. Tipton D. C. Williams D. M. Zisterer (2001) ArticleTitleOxidative stress induces apoptosis in C6 glioma cells: Involvement of mitogen-activated protein kinases and nuclear factor kappa B. Neurotox. Res 3 397–409

    Google Scholar 

  29. O. P. Mishra A. D. Zubrow Q. D. Ashraf (2004) ArticleTitleNitric oxide-mediated activation of extracellular signal regulated kinase (ERK) and cJUN N-terminal kinase (JNK) during hypoxia in cerebral cortical nuclei of newborn piglets. Neuroscience 124 179–186

    Google Scholar 

  30. S. Canals M. J. Casarejos S. Bernardo Particlede R. M. Solano M. A. Mena (2003) ArticleTitleSelective and persistent activation of extracellular signal-regulated protein kinase by nitric oxide in glial cells induces neuronal degeneration in glutathione- depleted midbrain cultures. Mol. Cell. Neurosci 24 1012–1026

    Google Scholar 

  31. C. R. Vargas M. Wajner L. R. Sirtori L. Goulart M. Chiochetta D. Coelho A. Latini S. Llesuy A. Bello-Klein R. Giugliani M. Deon C. F. Mello (2004) ArticleTitleEvidence that oxidative stress is increased in patients with X-linked adrenoleukodystrophy. Biochim. Biophys. Acta 1688 26–32

    Google Scholar 

  32. S. Ravid A. S. Diamond L. Eviatar (2000) ArticleTitleComa as an acute presentation of adrenoleukodystrophy. Pediatr. Neurol 22 237–239

    Google Scholar 

  33. J. A. Wilkinson I. J. Hopkins A. C. Pollard (1987) ArticleTitleCan head trauma influence the site of demyelination in adrenoleukodystrophy? Dev Med. Child Neurol 29 797–800

    Google Scholar 

  34. G. B. Luciani R. Pessotto A. Mazzucco (1997) ArticleTitleAdrenoleukodystrophy presenting as postperfusion syndrome (letter) N. Engl. J. Med 336 731–732

    Google Scholar 

  35. A. Di Biase S. Salvati R. Varì C. Avellino F. Sforza M. Cappa R. Masella (2000) ArticleTitleSusceptibility to oxidation of plasma low-density lipoprotein in X-linked adrenoleukodystrophy: Effects of simvastatin treatment. Mol. Genet. Metab 71 651–655

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Antonella Di Biase.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Biase, A.D., Benedetto, R.D., Salvati, S. et al. Effects of L-mono Methyl-arginine, N-Acetyl-cysteine and Diphenyleniodonium on Free Radical Release in C6 Glial Cells Enriched in Hexacosenoic Acid. Neurochem Res 30, 215–223 (2005). https://doi.org/10.1007/s11064-004-2444-8

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-004-2444-8

KEY WORDS

Navigation