Skip to main content

Advertisement

SpringerLink
Log in

Involvement of Nitric Oxide in Maneb- and Paraquat-Induced Parkinson’s Disease Phenotype in Mouse: Is There Any Link with Lipid Peroxidation?

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

The study aimed to investigate the involvement of nitric oxide (NO) in maneb (MB)- and paraquat (PQ)-induced Parkinson’s disease (PD) phenotype in mouse and its subsequent contribution to lipid peroxidation. Animals were treated intraperitoneally with or without MB and PQ, twice a week for 3, 6 and 9 weeks. In some sets of experiments (9 weeks treated groups), the animals were treated intraperitoneally with or without inducible nitric oxide synthase (iNOS) inhibitor-aminoguanidine, tyrosine kinase inhibitor-genistein, nuclear factor-kappa B (NF-kB) inhibitor-pyrrolidine dithiocarbamate (PDTC) or p38 mitogen activated protein kinase (MAPK) inhibitor-SB202190. Nitrite content and lipid peroxidation were measured in all treated groups along with respective controls. RNA was isolated from the striatum of control and treated mice and reverse transcribed into cDNA. RT-PCR was performed to amplify iNOS mRNA and western blot analysis was done to check its protein level. MB- and PQ-treatment induced nitrite content, expressions of iNOS mRNA and protein and lipid peroxidation as compared with respective controls. Aminoguanidine resulted in a significant attenuation of iNOS mRNA expression, nitrite content and lipid peroxidation demonstrating the involvement of nitric oxide in MB- and PQ-induced lipid peroxidation. Genistein, SB202190 and PDTC reduced the expression of iNOS mRNA, nitrite content and lipid peroxidation in MB- and PQ-treated mouse striatum. The results obtained demonstrate that nitric oxide contributes to an increase of MB- and PQ-induced lipid peroxidation in mouse striatum and tyrosine kinase, p38 MAPK and NF-kB regulate iNOS expression.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Marsden CD (1990) Parkinson’s disease. Lancet 335:948–952

    Article  CAS  PubMed  Google Scholar 

  2. Albin RL, Young AB, Penney JB (1989) The functional anatomy of basal ganglia disorders. Trends Neurosci 12:366–375

    Article  CAS  PubMed  Google Scholar 

  3. Singh MP, Patel S, Dikshit M et al (2006) Contribution of genomics and proteomics in understanding the role of modifying factors in Parkinson’s disease. Indian J Biochem Biophys 43:69–81

    CAS  PubMed  Google Scholar 

  4. Singh C, Ahmad I, Kumar A (2007) Pesticides and metals induced Parkinson’s disease: involvement of free radicals and oxidative stress. Cell Mol Biol 53:19–28

    CAS  PubMed  Google Scholar 

  5. Thiruchelvam M, Brockel BJ, Richfield EK et al (2000) Potentiated and preferential effects of combined paraquat and maneb on nigrostriatal dopamine systems: environmental risk factors for Parkinson’s disease? Brain Res 873:225–234

    Article  CAS  PubMed  Google Scholar 

  6. Cory-Slechta DA, Thiruchelvam M, Barlow BK et al (2005) Developmental pesticide models of the Parkinson disease phenotype. Environ Health Perspect 113:1263–1270

    Article  CAS  PubMed  Google Scholar 

  7. Patel S, Singh V, Kumar A et al (2006) Status of antioxidant defense system and expression of toxicant responsive genes in striatum of maneb-and paraquat-induced Parkinson’s disease phenotype in mouse: mechanism of neurodegeneration. Brain Res 1081:9–18

    Article  CAS  PubMed  Google Scholar 

  8. Kappus H (1986) Overview of enzyme systems involved in bio-reduction of drugs and in redox cycling. Biochem Pharmacol 35:1–6

    Article  CAS  PubMed  Google Scholar 

  9. Gragus Z, Klaassen CD (1996) Mechanisms of toxicity. In: Klaassen CD, Andur MO, Doull J (eds) Casarett and Doulls toxicology. The basic science of poisons. Macmillan, New York, pp 41–48

    Google Scholar 

  10. Beckman JS, Beckman TW, Chen J et al (1990) Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 87:1620–1624

    Article  CAS  PubMed  Google Scholar 

  11. Zhang J, Fitsanakis VA, Gu G et al (2003) Manganese ethylene-bis-dithiocarbamate and selective dopaminergic neurodegeneration in rat: a link through mitochondrial dysfunction. J Neurochem 84:336–346

    Article  CAS  PubMed  Google Scholar 

  12. Brooks AI, Chadwick CA, Gelbard HA et al (1999) Paraquat elicited neurobehavioral syndrome caused by dopaminergic neuron loss. Brain Res 823:1–10

    Article  CAS  PubMed  Google Scholar 

  13. McCormack AL, Thiruchelvam M, Manning-Bog AB et al (2002) Environmental risk factors and Parkinson’s disease: selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat. Neurobiol Dis 10:119–127

    Article  CAS  PubMed  Google Scholar 

  14. Thiruchelvam M, Richfield EK, Baggs RB et al (2000) The nigrostriatal dopaminergic system as a preferential target of repeated exposures to combined paraquat and maneb: implications for Parkinson’s disease. J Neurosci 20:9207–9214

    CAS  PubMed  Google Scholar 

  15. Patel S, Sinha A, Singh MP (2007) Identification of differentially expressed proteins in striatum of maneb-and paraquat-induced Parkinson’s disease phenotype in mouse. Neurotoxicol Teratol 29:578–585

    Article  CAS  PubMed  Google Scholar 

  16. Patel S, Singh K, Singh S et al (2008) Gene expression profiles of mouse striatum in control and maneb + paraquat-induced Parkinson’s disease phenotype: validation of differentially expressed energy metabolizing transcripts. Mol Biotechnol 40:59–68

    Article  CAS  PubMed  Google Scholar 

  17. Beckman JS (1996) Oxidative damage and tyrosine nitration from peroxynitrite. Chem Res Toxicol 9:836–844

    Article  CAS  PubMed  Google Scholar 

  18. Pryor WA, Squadrito GL (1995) The chemistry of peroxynitrite a product from the reaction of nitric oxide with superoxide. Am J Physiol 268:L699–L722

    CAS  PubMed  Google Scholar 

  19. Dawson VL, Dawson TM (1998) Nitric oxide in neurodegeneration. Prog Brain Res 118:215–229

    Article  CAS  PubMed  Google Scholar 

  20. Zhang L, Dawson VL, Dawson TM (2006) Role of nitric oxide in Parkinson’s disease. Pharmacol Ther 109:33–41

    Article  CAS  PubMed  Google Scholar 

  21. Liberatore GT, Jackson-Lewis V, Vukosavic S et al (1999) Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease. Nat Med 5:1403–1409

    Article  CAS  PubMed  Google Scholar 

  22. Paul A, Pendreigh RH, Plevin R (1995) Protein kinase C and tyrosine kinase pathways regulate lipopolysaccharide-induced nitric oxide synthase activity in RAW 264.7 murine macrophages. Br J Pharmacol 114:482–488

    CAS  PubMed  Google Scholar 

  23. Xu Z, Wang B, Wang X et al (2006) ERK1/2 and p38 mitogen-activated protein kinase mediate iNOS-induced spinal neuron degeneration after acute traumatic spinal cord injury. Life Sci 79:1895–1905

    Article  CAS  PubMed  Google Scholar 

  24. Koppal T, Drake J, Yatin S et al (1999) Peroxynitrite-induced alterations in synaptosomal membrane proteins: insights into oxidative stress in Alzheimer’s disease. J Neurochem 72:310–317

    Article  CAS  PubMed  Google Scholar 

  25. Liu W, Kato M, Itoigawa M et al (2001) Distinct involvement of NF-kB and p38 mitogen-activated protein kinase pathways in serum deprivation-mediated stimulation of inducible nitric oxide synthase and its inhibition by 4-hydroxynonenal. J Cell Biochem 83:271–280

    Article  CAS  PubMed  Google Scholar 

  26. Karpuzoglu E, Fenaux JB, Phillips RA et al (2006) Estrogen up-regulates inducible nitric oxide synthase, nitric oxide, and cyclooxygenase-2 in splenocytes activated with T cell stimulants: role of interferon-gamma. Endocrinology 147:662–671

    Article  CAS  PubMed  Google Scholar 

  27. Fan Q, Ding J, Zhang J et al (2004) Effect of the knockdown of podocin mRNA on nephrin and α-actinin in mouse podocyte. Exp Biol Med 229:964–970

    CAS  Google Scholar 

  28. Martin PY, Bianchi M, Roger F et al (2002) Arginine vasopressin modulates expression of neuronal NOS in rat renal medulla. Am J Physiol Renal Physiol 283:F559–F568

    CAS  PubMed  Google Scholar 

  29. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  30. Granger DL, Taintor RR, Boockvar KS, Hibbs JB (1996) Measurement of nitrate and nitrite in biological samples using nitrate reductase and Greiss reaction. Methods Enzymol 268:142–151

    Article  CAS  PubMed  Google Scholar 

  31. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  CAS  PubMed  Google Scholar 

  32. Singh S, Singh K, Patel DK et al (2009) The expression of CYP2D22, an ortholog of human CYP2D6, in mouse striatum and its modulation in MPTP-induced Parkinson’s disease phenotype and nicotine-mediated neuroprotection. Rejuvenation Res 12:185–197

    Article  CAS  PubMed  Google Scholar 

  33. Singh AK, Tiwari MN, Upadhyay G et al (2010) Long term exposure to cypermethrin induces the nigrostriatal dopaminergic neurodegeneration in adult rats: postnatal exposure enhances the susceptibility during adulthood. Neurobiol Aging. doi:10.1016/j.neurobiolaging.2010.02.018

  34. Ischiropoulos H, Al-Mehdi AB (1995) Peroxynitrite-mediated oxidative protein modifications. FEBS Lett 364:279–282

    Article  CAS  PubMed  Google Scholar 

  35. Przedborski S, Jackson-Lewis V, Djaldetti R et al (2000) The parkinsonian toxin MPTP: action and mechanism. Restor Neurol Neurosci 16:135–142

    CAS  PubMed  Google Scholar 

  36. Torreilles F, Salman-Tabcheh S, Guerin M, Torreilles J (1999) Neurodegenerative disorders: the role of peroxynitrite. Brain Res Rev 30:153–163

    Article  CAS  PubMed  Google Scholar 

  37. Okuno T, Nakatsuji Y, Kumanogoh A et al (2005) Loss of dopaminergic neurons by the induction of inducible nitric oxide synthase and cyclooxygenase-2 via CD40: relevance to Parkinson’s disease. J Neurosci Res 81:874–882

    Article  CAS  PubMed  Google Scholar 

  38. Knott C, Stern G, Wilkin GP (2000) Inflammatory regulators in Parkinson’s disease: iNOS, lipocortin-I and cyclooxygenases-1 and -2. Mol Cell Neurosci 16:724–739

    Article  CAS  PubMed  Google Scholar 

  39. Bus JS, Gibson JE (1984) Paraquat: model for oxidant-initiated toxicity. Environ Health Perspect 55:37–46

    Article  CAS  PubMed  Google Scholar 

  40. Cohen GM, d’Arcy Doherty M (1987) Free radical mediated cell toxicity by redox cycling chemicals. Br J Cancer Suppl 8:46–52

    CAS  PubMed  Google Scholar 

  41. Good PF, Hsu A, Werner P et al (1998) Protein nitration in Parkinson’s disease. J Neurophathol Exp Neurol 57:338–342

    Article  CAS  Google Scholar 

  42. Dehmer T, Lindenau J, Haid S et al (2000) Deficiency of inducible nitric oxide synthase protects against MPTP toxicity in vivo. J Neurochem 74:2213–2216

    Article  CAS  PubMed  Google Scholar 

  43. Chen YQ, Fisher JH, Wang MH (1998) Activation of the RON receptor tyrosine Kinase inhibits inducible nitric oxide synthase (iNOS) expression by murine peritoneal exudate macrophages: phosphatidylinositol-3 kinase is required for RON-mediated inhibition of iNOS expression. J Immun 161:4950–4959

    CAS  PubMed  Google Scholar 

  44. Noack H, Possel H, Rethfeldt C et al (1999) Peroxynitrite mediated damage and lowered superoxide tolerance in primary cortical glial cultures after induction of the inducible isoform of NOS. Glia 28:13–24

    Article  CAS  PubMed  Google Scholar 

  45. Denicola A, Radi R (2005) Peroxynitrite and drug-dependent toxicity. Toxicology 208:273–288

    Article  CAS  PubMed  Google Scholar 

  46. Antunes F, Nunes C, Laranjinha J, Cadenas E (2005) Redox interactions of nitric oxide with dopamine and its derivatives. Toxicology 208:207–212

    Article  CAS  PubMed  Google Scholar 

  47. Brown GC (1999) Nitric oxide and mitochondrial respiration. Biochim Biophys Acta 1411:351–369

    Article  CAS  PubMed  Google Scholar 

  48. Violi F, Marino R, Milite MT, Loffredo L (1999) Nitric oxide and its role in lipid peroxidation. Diabetes Metab Res Rev 15:283–288

    Article  CAS  PubMed  Google Scholar 

  49. Giardino I, Fard AK, Hatchell DL, Brownlee M (1998) Aminoguanidine inhibits reactive oxygen species formation, lipid peroxidation, and oxidant-induced apoptosis. Diabetes 47:1114–1120

    Article  CAS  PubMed  Google Scholar 

  50. Kedziora-Kornatowska KZ, Luciak M, Blaszczyk J, Pawlak W (1998) Effect of aminoguanidine on the generation of superoxide anion and nitric oxide by peripheral blood granulocytes of rats with streptozotocin-induced diabetes. Clin Chim Acta 278:45–53

    Article  CAS  PubMed  Google Scholar 

  51. Courderot-Masuyer C, Dalloz F, Maupoil V, Rochette L (1999) Antioxidant properties of aminoguanidine. Fundan Clin Pharmacol 13:535–540

    Article  CAS  Google Scholar 

  52. Tsang AH, Lee YI, Ko HS et al (2009) S-nitrosylation of XIAP compromises neuronal survival in Parkinson’s disease. ProcNatl Acad Sci USA 106:4900–4905

    Article  CAS  Google Scholar 

  53. Padovan-Neto FE, Echeverry MB, Tumas V et al (2009) Nitric oxide synthase inhibition attenuates L-DOPA-induced dyskinesias in a rodent model of Parkinson’s disease. Neuroscience 159:927–935

    Article  CAS  PubMed  Google Scholar 

  54. Vallance P, Leiper J (2002) Blocking NO synthesis: how, where and why? Nat Rev Drug Discov 1:939–950

    Article  CAS  PubMed  Google Scholar 

  55. Kong LY, McMillian MK, Maronpot R, Hong JS (1996) Protein tyrosine kinase inhibitors suppress the production of nitric oxide in mixed glia, microglia-enriched or astrocyte-enriched cultures. Brain Res 729:102–109

    Article  CAS  PubMed  Google Scholar 

  56. Jeohn GH, Cooper CL, Wilson B et al (2002) p38 MAP kinase is involved in lipopolysaccharide-induced dopaminergic neuronal cell death in rat mesencephalic neuron-glia cultures. Ann NY Acad Sci 962:332–346

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors sincerely thank Department of Biotechnology (DBT) for the financial support of the study. Authors acknowledge Council of Scientific and Industrial Research (CSIR), New Delhi, India for providing research fellowships to Suman Patel, Sharawan Yadav and Anand Kumar Singh. Authors also thank University Grants Commission (UGC), New Delhi, India for providing research fellowship to Seema Singh. The IITR communication number of this article is 2780.

Author information

Authors and Affiliations

  1. Indian Institute of Toxicology Research (Council of Scientific and Industrial Research), Mahatma Gandhi Marg, Post Box-80, Lucknow, 226 001, UP, India

    Satya Prakash Gupta, Suman Patel, Sharawan Yadav, Anand Kumar Singh, Seema Singh & Mahendra Pratap Singh

Authors
  1. Satya Prakash Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Suman Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sharawan Yadav
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anand Kumar Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Seema Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mahendra Pratap Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mahendra Pratap Singh.

Additional information

Satya Prakash Gupta and Suman Patel have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gupta, S.P., Patel, S., Yadav, S. et al. Involvement of Nitric Oxide in Maneb- and Paraquat-Induced Parkinson’s Disease Phenotype in Mouse: Is There Any Link with Lipid Peroxidation?. Neurochem Res 35, 1206–1213 (2010). https://doi.org/10.1007/s11064-010-0176-5

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-010-0176-5

Keywords

Search

Navigation