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Metalloproteinase’s Activity and Oxidative Stress in Mild Cognitive Impairment and Alzheimer’s Disease

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Abstract

Matrix metalloproteinases (MMPs) and oxidative stress have been implicated in neurological diseases such as Alzheimer’s disease (AD). Plasma MMP-2 and MMP-9 activities were assessed in Mild Cognitive Impairment (MCI) and AD subjects compared with aged-matched controls, and subsequently analysed in relation to oxidative stress markers. Both MMP-2 and MMP-9 showed no significant changes versus control subjects. Plasma glutathione peroxidase Se-dependent (GPx-Se) activity and malondialdehyde (MDA) levels were higher in AD than in controls (P < 0.05), suggesting a role for GPx-Se in controlling oxidative stress in AD. Negative correlations were observed between MMPs and MDA in AD and MCI patients (P < 0.05). In conclusion, oxidative stress events did not include activation of MMPs and this similar pattern in AD and MCI suggests that both are biochemically equivalent.

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References

  1. Lorenzl S, Albers DS, LeWitt PA et al (2003) Tissue inhibitors of matrix metalloproteinases are elevated in cerebrospinal fluid of neurodegenerative diseases. J Neurol Sci 207:71–76. doi:10.1016/S0022-510X(02)00398-2

    Article  PubMed  CAS  Google Scholar 

  2. Yong VW, Krekoski CA, Forsyth PA et al (1998) Matrix metalloproteinases and diseases of the cns. Trends Neurosci 21:75–80. doi:10.1016/S0166-2236(97)01169-7

    Article  PubMed  CAS  Google Scholar 

  3. Szklarczyk A, Lapinska J, Rylski M et al (2002) Matrix metalloproteinase-9 undergoes expression and activation during dendritic remodeling in adult hippocampus. J Neurosci 22:920–930

    PubMed  CAS  Google Scholar 

  4. Jourquin J, Tremblay E, Decanis N et al (2003) Neuronal activity-dependent increase of net matrix metalloproteinase activity is associated with MMP-9 neurotoxicity after kainate. Eur J NeuroSci 18:1507–1517. doi:10.1046/j.1460-9568.2003.02876.x

    Article  PubMed  Google Scholar 

  5. Wright JW, Masino AJ, Reichert JR et al (2003) Ethanol-induced impairment of spatial memory and brain matrix metalloproteinases. Brain Res 963:252–261. doi:10.1016/S0006-8993(02)04036-2

    Article  PubMed  CAS  Google Scholar 

  6. Zhang JW, Deb S, Gottschall PE (1998) Regional and differential expression of gelatinases in rat brain after systemic kainic acid or bicuculline administration. Eur J NeuroSci 10:3358–3368. doi:10.1046/j.1460-9568.1998.00347.x

    Article  PubMed  CAS  Google Scholar 

  7. Backstrom JR, Lim GP, Cullen MJ et al (1996) Matrix metalloproteinase-9 (MMP-9) is synthesized in neurons of the human hippocampus and is capable of degrading the amyloid-beta peptide (1–40). J Neurosci 16:7910–7919

    PubMed  CAS  Google Scholar 

  8. Yushchenko M, Weber F, Mader M et al (2000) Matrix metalloproteinase-9 (MMP-9) in human cerebrospinal fluid (CSF): elevated levels are primarily related to CSF cell count. J Neuroimmunol 110:244–251. doi:10.1016/S0165-5728(00)00339-8

    Article  PubMed  CAS  Google Scholar 

  9. Szabo KA, Ablin RJ, Singh G (2004) Matrix metalloproteinases and the immune response. Clin Appl Immunol Rev 4:295–319. doi:10.1016/j.cair.2004.02.001

    Article  CAS  Google Scholar 

  10. Peress N, Perillo E, Zucker S (1995) Localization of tissue inhibitor of matrix metalloproteinases in alzheimer’s disease and normal brain. J Neuropathol Exp Neurol 54:16–22. doi:10.1097/00005072-199501000-00002

    Article  PubMed  CAS  Google Scholar 

  11. Ma Z, Chang MJ, Shah RC et al (2005) Interferon-gamma-activated stat-1alpha suppresses MMP-9 gene transcription by sequestration of the coactivators cbp/p300. J Leukoc Biol 78:515–523. doi:10.1189/jlb.0205112

    Article  PubMed  CAS  Google Scholar 

  12. Li J, Leschka S, Rutschow S et al (2007) Immunomodulation by interleukin-4 suppresses matrix metalloproteinases and improves cardiac function in murine myocarditis. Eur J Pharmacol 554:60–68. doi:10.1016/j.ejphar.2006.08.024

    Article  PubMed  CAS  Google Scholar 

  13. Stearns ME, Wang M, Hu Y et al (2003) Interleukin 10 blocks matrix metalloproteinase-2 and membrane type 1-matrix metalloproteinase synthesis in primary human prostate tumor lines. Clin Cancer Res 9:1191–1199

    PubMed  CAS  Google Scholar 

  14. Schroen DJ, Brinckerhoff CE (1996) Nuclear hormone receptors inhibit matrix metalloproteinase (MMP) gene expression through diverse mechanisms. Gene Expr 6:197–207

    PubMed  CAS  Google Scholar 

  15. Shi Q, Gibson GE (2007) Oxidative stress and transcriptional regulation in Alzheimer disease. Alzheimer Dis Assoc Disord 21:276–291

    PubMed  CAS  Google Scholar 

  16. Golubkov VS, Chekanov AV, Shiryaev SA et al (2007) Proteolysis of the membrane type-1 matrix metalloproteinase prodomain: Implications for a two-step proteolytic processing and activation. J Biol Chem 282:36283–36291. doi:10.1074/jbc.M706290200

    Article  PubMed  CAS  Google Scholar 

  17. Rosenblum G, Meroueh S, Toth M et al (2007) Molecular structures and dynamics of the stepwise activation mechanism of a matrix metalloproteinase zymogen: Challenging the cysteine switch dogma. J Am Chem Soc 129:13566–13574. doi:10.1021/ja073941l

    Article  PubMed  CAS  Google Scholar 

  18. Fu X, Parks WC, Heinecke JW (2008) Activation and silencing of matrix metalloproteinases. Semin Cell Dev Biol 19:2–13. doi:10.1016/j.semcdb.2007.06.005

    Article  PubMed  CAS  Google Scholar 

  19. Bermejo P, Martin-Aragon S, Benedi J et al (2008) Peripheral levels of glutathione and protein oxidation as markers in the development of Alzheimer’s disease from mild cognitive impairment. Free Radic Res 42:162–170. doi:10.1080/10715760701861373

    Article  PubMed  CAS  Google Scholar 

  20. Petersen RC, Doody R, Kurz A et al (2001) Current concepts in mild cognitive impairment. Arch Neurol 58:1985–1992. doi:10.1001/archneur.58.12.1985

    Article  PubMed  CAS  Google Scholar 

  21. McKhann G, Drachman D, Folstein M et al (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force on Alzheimer’s disease. Neurology 34:939–944

    PubMed  CAS  Google Scholar 

  22. Tinetti ME (1986) Performance-oriented assessment of mobility problems in elderly patients. J Am Geriatr Soc 34:119–126

    PubMed  CAS  Google Scholar 

  23. Ankri J, Andrieu S, Beaufils B et al (2005) Beyond the global score of the Zarit burden interview: useful dimensions for clinicians. Int J Geriatr Psychiatry 20:254–260. doi:10.1002/gps.1275

    Article  PubMed  Google Scholar 

  24. Cockrell JR, Folstein MF (1988) Mini-mental state examination (MMSE). Psychopharmacol Bull 24:689–692

    PubMed  CAS  Google Scholar 

  25. Schmand B, Walstra G, Lindeboom J et al (2000) Early detection of Alzheimer’s disease using the Cambridge cognitive examination (CAMCOG). Psychol Med 30:619–627. doi:10.1017/S0033291799002068

    Article  PubMed  CAS  Google Scholar 

  26. Makatura TJ, Lam CS, Leahy BJ et al (1999) Standardized memory tests and the appraisal of everyday memory. Brain Inj 13:355–367. doi:10.1080/026990599121548

    Article  PubMed  CAS  Google Scholar 

  27. Cummings JL, Mega M, Gray K et al (1994) The neuropsychiatric inventory: comprehensive assessment of psychopathology in dementia. Neurology 44:2308–2314

    PubMed  CAS  Google Scholar 

  28. Torres RM, Miralles R, Garcia-Caselles MP et al (2004) Observational scale and geriatric depression scale of Yesavage to identify depressive symptoms in older patients. Arch Gerontol Geriatr Suppl (9):437–442

  29. Ready RE, Ott BR, Grace J et al (2002) The cornell-brown scale for quality of life in dementia. Alzheimer Dis Assoc Disord 16:109–115. doi:10.1097/00002093-200204000-00008

    Article  PubMed  Google Scholar 

  30. Kleiner DE, Stetler-Stevenson WG (1994) Quantitative zymography: detection of picogram quantities of gelatinases. Anal Biochem 218:325–329. doi:10.1006/abio.1994.1186

    Article  PubMed  CAS  Google Scholar 

  31. Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169

    PubMed  CAS  Google Scholar 

  32. Hill HD, Straka JG (1988) Protein determination using bicinchoninic acid in the presence of sulfhydryl reagents. Anal Biochem 170:203–208. doi:10.1016/0003-2697(88)90109-1

    Article  PubMed  CAS  Google Scholar 

  33. Barja de Quiroga G, Perez-Campo R, Lopez Torres M (1990) Anti-oxidant defences and peroxidation in liver and brain of aged rats. Biochem J 272:247–250

    PubMed  CAS  Google Scholar 

  34. Bermejo P, Gomez-Serranillos P, Santos J et al (1997) Determination of malonaldehyde in Alzheimer’s disease: a comparative study of high-performance liquid chromatography and thiobarbituric acid test. Gerontology 43:218–222

    Article  PubMed  CAS  Google Scholar 

  35. Kelly PJ, Morrow JD, Ning M et al (2008) Oxidative stress and matrix metalloproteinase-9 in acute ischemic stroke: the biomarker evaluation for antioxidant therapies in stroke (beat-stroke) study. Stroke 39:100–104. doi:10.1161/STROKEAHA.107.488189

    Article  PubMed  CAS  Google Scholar 

  36. Tsai HC, Chung LY, Chen ER et al (2008) Association of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-4 in cerebrospinal fluid with blood–brain barrier dysfunction in patients with eosinophilic meningitis caused by Angiostrongylus cantonensis. Am J Trop Med Hyg 78:20–27

    PubMed  CAS  Google Scholar 

  37. Lorenzl S, Albers DS, Relkin N et al (2003) Increased plasma levels of matrix metalloproteinase-9 in patients with Alzheimer’s disease. Neurochem Int 43:191–196. doi:10.1016/S0197-0186(03)00004-4

    Article  PubMed  CAS  Google Scholar 

  38. Baig S, Kehoe PG, Love S (2008) MMP-2, -3 and -9 levels and activity are not related to Abeta load in the frontal cortex in Alzheimer’s disease. Neuropathol Appl Neurobiol 34:205–215. doi:10.1111/j.1365-2990.2007.00897.x

    Article  PubMed  CAS  Google Scholar 

  39. Adair JC, Charlie J, Dencoff JE et al (2004) Measurement of gelatinase B (MMP-9) in the cerebrospinal fluid of patients with vascular dementia and Alzheimer disease. Stroke 35:e159–e162. doi:10.1161/01.STR.0000127420.10990.76

    Article  PubMed  CAS  Google Scholar 

  40. Farooqui AA, Ong WY, Horrocks LA (2004) Biochemical aspects of neurodegeneration in human brain: involvement of neural membrane phospholipids and phospholipases A2. Neurochem Res 29:1961–1977. doi:10.1007/s11064-004-6871-3

    Article  PubMed  CAS  Google Scholar 

  41. Chance B, Sies H, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 59:527–605

    PubMed  CAS  Google Scholar 

  42. John M, Jaworski C, Chen Z et al (2004) Matrix metalloproteinases are down-regulated in rat lenses exposed to oxidative stress. Exp Eye Res 79:839–846. doi:10.1016/j.exer.2004.08.025

    Article  PubMed  CAS  Google Scholar 

  43. Ganguly K, Kundu P, Banerjee A et al (2006) Hydrogen peroxide-mediated downregulation of matrix metalloprotease-2 in indomethacin-induced acute gastric ulceration is blocked by melatonin and other antioxidants. Free Radic Biol Med 41:911–925. doi:10.1016/j.freeradbiomed.2006.04.022

    Article  PubMed  CAS  Google Scholar 

  44. Straface E, Matarrese P, Gambardella L et al (2005) Oxidative imbalance and cathepsin D changes as peripheral blood biomarkers of Alzheimer disease: a pilot study. FEBS Lett 579:2759–2766. doi:10.1016/j.febslet.2005.03.094

    Article  PubMed  CAS  Google Scholar 

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Acknowledgement

This work was financially supported by a grant (PI021745) from the National Research Foundation of the Spanish Ministry of Health (FIS).

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Authors and Affiliations

  1. Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid, Avenida de la Complutense s/n, 28040, Madrid, Spain

    Sagrario Martín-Aragón, Paloma Bermejo-Bescós, Juana Benedí, Emanuela Felici & Ángel Ma Villar

  2. Servicio de Geriatría, Hospital Universitario Clínico San Carlos, C/Profesor Martín Lagos s/n, 28040, Madrid, Spain

    Pedro Gil & José Manuel Ribera

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  1. Sagrario Martín-Aragón
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Correspondence to Sagrario Martín-Aragón.

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Martín-Aragón, S., Bermejo-Bescós, P., Benedí, J. et al. Metalloproteinase’s Activity and Oxidative Stress in Mild Cognitive Impairment and Alzheimer’s Disease. Neurochem Res 34, 373–378 (2009). https://doi.org/10.1007/s11064-008-9789-3

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  • DOI: https://doi.org/10.1007/s11064-008-9789-3

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