Skip to main content

Advertisement

Log in

Protein Levels and Activity of Some Antioxidant Enzymes in Hippocampus of Subjects with Amnestic Mild Cognitive Impairment

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

Abstract

Mild cognitive impairment (MCI) is generally referred to the transitional zone between normal cognitive aging and early dementia or clinically probable Alzheimer’s disease (AD). Most individuals with amnestic MCI eventually develop AD, which suggests that MCI may be the earliest phase of AD. Oxidative stress is observed in brain from subjects with both AD and MCI. Among others, two possibilities for elevated oxidataive stress are decreased activity or elevated expression of antioxidant enzymes, the latter as a response to the former. Accordingly, in the current study, the protein levels and activity of some antioxidant enzymes in the hippocampus of control and MCI brain were measured using Western blot analysis and spectrophotometric methods, respectively. Alterations in the levels and activity of a number of antioxidant enzymes in MCI brain compared to age-matched controls were found. These results are consistent with the hypothesis that oxidative stress may be an early event in the progression of amnestic MCI to AD.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Chetelat G, Desgranges B, de la Sayette V et al (2004) [At the boundary between normal aging and Alzheimer disease]. Rev Neurol (Paris) 160:S55–S63

    CAS  Google Scholar 

  2. Petersen RC (2000) Mild cognitive impairment: transition between aging and Alzheimer’s disease. Neurologia 15:93–101

    Article  PubMed  CAS  Google Scholar 

  3. Petersen RC (2004) Mild cognitive impairment as a diagnostic entity. J Intern Med 256:183–194

    Article  PubMed  CAS  Google Scholar 

  4. Portet F, Ousset PJ, Touchon J (2005) [What is a mild cognitive impairment?]. Rev Prat 55:1891–1894

    PubMed  Google Scholar 

  5. Butterfield DA, Poon HF, St Clair D et al (2006) Redox proteomics identification of oxidatively modified hippocampal proteins in mild cognitive impairment: insights into the development of Alzheimer’s disease. Neurobiol Dis 22:223–232

    Article  PubMed  CAS  Google Scholar 

  6. Butterfield DA, Reed T, Perluigi M et al (2006) Elevated protein-bound levels of the lipid peroxidation product, 4-hydroxy-2-nonenal, in brain from persons with mild cognitive impairment. Neurosci Lett 397:170–173

    Article  PubMed  CAS  Google Scholar 

  7. Butterfield DA, Reed TT, Perluigi M et al (2007) Elevated levels of 3-Nitrotyrosine in brain from subjects with amnestic mild cognitive impairment: implications for the role of nitration in the progression of Alzheimer’s disease. Brain Res 1148:243–248

    Article  PubMed  CAS  Google Scholar 

  8. Keller JN, Schmitt FA, Scheff SW et al (2005) Evidence of increased oxidative damage in subjects with mild cognitive impairment. Neurology 64:1152–1156

    PubMed  CAS  Google Scholar 

  9. Wang J, Markesbery WR, Lovell MA (2006) Increased oxidative damage in nuclear and mitochondrial DNA in mild cognitive impairment. J Neurochem 96:825–832

    Article  PubMed  CAS  Google Scholar 

  10. Halliwell B (1992) Reactive oxygen species and the central nervous system. J Neurochem 59:1609–1623

    Article  PubMed  CAS  Google Scholar 

  11. Halliwell B (1992) Oxygen radicals as key mediators in neurological disease: fact or fiction? Ann Neurol 32(Suppl):S10–S15

    Article  PubMed  CAS  Google Scholar 

  12. Cooper AJ, Kristal BS (1997) Multiple roles of glutathione in the central nervous system. Biol Chem 378:793–802

    PubMed  CAS  Google Scholar 

  13. Meister A, Anderson ME (1983) Glutathione. Annu Rev Biochem 52:711–760

    Article  PubMed  CAS  Google Scholar 

  14. Joshi G, Hardas S, Sultana R et al (2007) Glutathione elevation by gamma-glutamyl cysteine ethyl ester as a potential therapeutic strategy for preventing oxidative stress in brain mediated by in vivo administration of adriamycin: implication for chemobrain. J Neurosci Res 85:497–503

    Article  PubMed  CAS  Google Scholar 

  15. Bains JS, Shaw CA (1997) Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death. Brain Res Brain Res Rev 25:335–358

    Article  PubMed  CAS  Google Scholar 

  16. Calabrese V, Sultana R, Scapagnini G et al (2006) Nitrosative stress, cellular stress response, and thiol homeostasis in patients with Alzheimer’s disease. Antioxid Redox Signal 8:1975–1986

    Article  PubMed  CAS  Google Scholar 

  17. Esterbauer H, Schaur RJ, Zollner H (1991) Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 11:81–128

    Article  PubMed  CAS  Google Scholar 

  18. Sultana R, Butterfield DA (2004) Oxidatively modified GST and MRP1 in Alzheimer’s disease brain: implications for accumulation of reactive lipid peroxidation products. Neurochem Res 29:2215–2220

    Article  PubMed  CAS  Google Scholar 

  19. Renes J, de Vries EG, Nienhuis EF et al (1999) ATP- and glutathione-dependent transport of chemotherapeutic drugs by the multidrug resistance protein MRP1. Br J Pharmacol 126:681–688

    Article  PubMed  CAS  Google Scholar 

  20. Lovell MA, Xie C, Markesbery WR (1998) Decreased glutathione transferase activity in brain and ventricular fluid in Alzheimer’s disease. Neurol 51:1562–1566

    CAS  Google Scholar 

  21. Carlberg I, Mannervik B (1985) Glutathione reductase. Methods Enzymol 113:484–490

    Article  PubMed  CAS  Google Scholar 

  22. Habig WH, Jakoby WB (1981) Assays for differentiation of glutathione S-transferases. Methods Enzymol 77:398–405

    Article  PubMed  CAS  Google Scholar 

  23. Butterfield DA, Reed T, Newman SF, Sultana R (2007) Roles of amyloid beta-peptide-associated oxidative stress and brain protein modifications in the pathogenesis of Alzheimer’s disease and mild cognitive impairment. Free Radic Biol Med 43:658–677

    Article  PubMed  CAS  Google Scholar 

  24. Sultana R, Reed T, Perluigi M et al (2007) Proteomic identification of nitrated brain proteins in amnestic mild cognitive impairment: a regional study. J Cell Mol Med 11:839–851

    Article  PubMed  CAS  Google Scholar 

  25. Benzi G, Moretti A (1995) Age- and peroxidative stress-related modifications of the cerebral enzymatic activities linked to mitochondria and the glutathione system. Free Radic Biol Med 19:77–101

    Article  PubMed  CAS  Google Scholar 

  26. Palmer AM (1999) The activity of the pentose phosphate pathway is increased in response to oxidative stress in Alzheimer’s disease. J Neural Transm 106:317–328

    Article  PubMed  CAS  Google Scholar 

  27. Townsend DM, Tew KD, Tapiero H (2003) The importance of glutathione in human disease. Biomed Pharmacother 57:145–155

    Article  PubMed  CAS  Google Scholar 

  28. Sies H (1999) Glutathione and its role in cellular functions. Free Radic Biol Med 27:916–921

    Article  PubMed  CAS  Google Scholar 

  29. Schuessel K, Leutner S, Cairns NJ et al (2004) Impact of gender on upregulation of antioxidant defence mechanisms in Alzheimer’s disease brain. J Neural Transm 111:1167–1182

    Article  PubMed  CAS  Google Scholar 

  30. Maier CM, Chan PH (2002) Role of superoxide dismutases in oxidative damage and neurodegenerative disorders. Neuroscientist 8:323–334

    PubMed  CAS  Google Scholar 

  31. Noor R, Mittal S, Iqbal J (2002) Superoxide dismutase—applications and relevance to human diseases. Med Sci Monit 8:RA210–RA215

    PubMed  CAS  Google Scholar 

  32. Kishida KT, Klann E (2007) Sources and targets of reactive oxygen species in synaptic plasticity and memory. Antioxid Redox Signal 9:233–44

    Article  PubMed  CAS  Google Scholar 

  33. Castegna A, Aksenov M, Aksenova M et al (2002) Proteomic identification of oxidatively modified proteins in Alzheimer’s disease brain. Part I: creatine kinase BB, glutamine synthase, and ubiquitin carboxy-terminal hydrolase L-1. Free Radic Biol Med. 33:562–571

    Article  PubMed  CAS  Google Scholar 

  34. Castegna A, Aksenov M, Thongboonkerd V et al (2002) Proteomic identification of oxidatively modified proteins in Alzheimer’s disease brain. Part II: dihydropyrimidinase-related protein 2, alpha-enolase and heat shock cognate 71. J Neurochem 82:1524–1532

    Article  PubMed  CAS  Google Scholar 

  35. Castegna A, Thongboonkerd V, Klein JB et al (2003) Proteomic identification of nitrated proteins in Alzheimer’s disease brain. J Neurochem 85:1394–1401

    Article  PubMed  CAS  Google Scholar 

  36. Sultana R, Boyd-Kimball D, Poon HF et al (2006) Redox proteomics identification of oxidized proteins in Alzheimer’s disease hippocampus and cerebellum: an approach to understand pathological and biochemical alterations in AD. Neurobiol Aging 27:1564–1576

    Article  PubMed  CAS  Google Scholar 

  37. Sultana R, Poon HF, Cai J et al (2006) Identification of nitrated proteins in Alzheimer’s disease brain using a redox proteomics approach. Neurobiol Dis 22:76–87

    Article  PubMed  CAS  Google Scholar 

  38. Rinaldi P, Polidori MC, Metastasio A et al (2003) Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer’s disease. Neurobiol Aging 24:915–919

    Article  PubMed  CAS  Google Scholar 

  39. Butterfield D, Castegna A, Pocernich C et al (2002) Nutritional approaches to combat oxidative stress in Alzheimer’s disease. J Nutr Biochem 13:444

    Article  PubMed  CAS  Google Scholar 

  40. Anderson ME, Luo JL (1998) Glutathione therapy: from prodrugs to genes. Semin Liver Dis 18:415–424

    Article  PubMed  CAS  Google Scholar 

  41. Mancuso C, Bates TE, Butterfield DA et al (2007) Natural antioxidants in Alzheimer’s disease. Expert Opin Investig Drugs 16:1921–1931

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank the faculty of the UK ADC for providing the brain specimens used for this study. This research was supported in part by NIH grants to D.A.B [AG-05119, AG-10836].

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to D. Allan Butterfield.

Additional information

Special issue article in honor of Dr. Anna Maria Giuffrida-Stella.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sultana, R., Piroddi, M., Galli, F. et al. Protein Levels and Activity of Some Antioxidant Enzymes in Hippocampus of Subjects with Amnestic Mild Cognitive Impairment. Neurochem Res 33, 2540–2546 (2008). https://doi.org/10.1007/s11064-008-9593-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-008-9593-0

Keywords

Navigation