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In Vitro Effect of H2O2, Some Transition Metals and Hydroxyl Radical Produced Via Fenton and Fenton-Like Reactions, on the Catalytic Activity of AChE and the Hydrolysis of ACh

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Abstract

It is well known that the principal biomolecules involved in Alzheimer’s disease (AD) are acetylcholinesterase (AChE), acetylcholine (ACh) and the amyloid beta peptide of 42 amino acid residues (Aβ42). ACh plays an important role in human memory and learning, but it is susceptible to hydrolysis by AChE, while the aggregation of Aβ42 forms oligomers and fibrils, which form senile plaques in the brain. The Aβ42 oligomers are able to produce hydrogen peroxide (H2O2), which reacts with metals (Fe2+, Cu2+, Cr3+, Zn2+, and Cd2+) present at high concentrations in the brain of AD patients, generating the hydroxyl radical (·OH) via Fenton (FR) and Fenton-like (FLR) reactions. This mechanism generates high levels of free radicals and, hence, oxidative stress, which has been correlated with the generation and progression of AD. Therefore, we have studied in vitro how AChE catalytic activity and ACh levels are affected by the presence of metals (Fe3+, Cu2+, Cr3+, Zn2+, and Cd2+), H2O2 (without Aβ42), and ·OH radicals produced from FR and FLR. The results showed that the H2O2 and the metals do not modify the AChE catalytic activity, but the ·OH radical causes a decrease in it. On the other hand, metals, H2O2 and ·OH radicals, increase the ACh hydrolysis. This finding suggests that when H2O2, the metals and the ·OH radicals are present, both, the AChE catalytic activity and ACh levels diminish. Furthermore, in the future it may be interesting to study whether these effects are observed when H2O2 is produced directly from Aβ42.

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References

  1. Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM (2007) Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement 3:186–191

    Article  PubMed  Google Scholar 

  2. Talesa VN (2001) Acetylcholinesterase in Alzheimer’s disease. Mech Ageing Dev 122:1961–1969

    Article  PubMed  CAS  Google Scholar 

  3. Lanctôt KL, Herrmann N, Yau KK, Khan LR, Liu BA, LouLou MM, Einarson TR (2003) Efficacy and safety of cholinesterase inhibitors in Alzheimer’s disease: a meta-analysis. CMAJ 169:557–564

    PubMed  PubMed Central  Google Scholar 

  4. Inestrosa NC, Urra S, Colombres M (2004) Acetylcholinesterase (AChE)–amyloid-beta-peptide complexes in Alzheimer’s disease. The Wnt signaling pathway. Curr Alzheimer Res 1:249–254

    Article  PubMed  CAS  Google Scholar 

  5. Akatsu H, Hori A, Yamamoto T, Yoshida M, Mimuro M, Hashizume Y, Tooyama I, Yezdimer EM (2012) Transition metal abnormalities in progressive dementias. Biometals 25:337–350

    Article  PubMed  CAS  Google Scholar 

  6. Hureau Ch (2012) Coordination of redox active metal ions to the amyloid precursor protein and to amyloid-beta peptides involved in Alzheimer disease. Part 1: An overview. Coord Chem Rev 256:2164–2174

    Article  CAS  Google Scholar 

  7. Panayi AE, Spyrou NM, Iversen BS, White MA, Part P (2002) Determination of cadmium and zinc in Alzheimer’s brain tissue using inductively coupled plasma mass spectrometry. J Neurol Sci 195:1–10

    Article  PubMed  CAS  Google Scholar 

  8. El-Yazigi A, Martin CR, Siqueira EB (1988) Concentrations of chromium, cesium, and tin in cerebrospinal fluid of patients with brain neoplasms, leukemia or other noncerebral malignancies, and neurological diseases. Clin Chem 34:1084–1086

    PubMed  CAS  Google Scholar 

  9. Pretto A, Loro VL, Morsch VM, Moraes BS, Menezes Ch, Clasen B, Hoehne L, Dressler V (2010) Acetylcholinesterase activity, lipid peroxidation, and bioaccumulation in silver catfish (Rhamdia quelen) exposed to cadmium. Arch Environ Contam Toxicol 58:1008–1014

    Article  PubMed  CAS  Google Scholar 

  10. Sant’Anna MC, Soares V de M, Seibt KJ, Ghisleni G, Rico EP, Rosemberg DB, de Oliveira JR, Schröder N, Bonan CD, Bogo MR (2011) Iron exposure modifies acetylcholinesterase activity in zebrafish (Danio rerio) tissues: distinct susceptibility of tissues to iron overload. Fish Physiol Biochem 37:573–581

  11. Tabner BJ, Turnbull S, King JE, Benson FE, El-Agnaf OMA, Allsop D (2006) A spectroscopic study of some of the peptidyl radicals formed following hydroxyl radical attack on beta-amyloid and alpha-synuclein. Free Radic Res 40:731–739

    Article  PubMed  CAS  Google Scholar 

  12. Butterfield DA (2003) Amyloid beta-peptide [1-42]-associated free radical-induced oxidative stress and neurodegeneration in Alzheimer’s disease brain: mechanisms and consequences. Cur Med Chem 10:2651–2659

    Article  CAS  Google Scholar 

  13. Nadal RC, Rigby SEJ, Viles JH (2008) Amyloid beta-Cu2+ complexes in both monomeric and fibrillar forms do not generate H2O2 catalytically but quench hydroxyl radicals. Biochemistry 47:11653–11664

    Article  PubMed  CAS  Google Scholar 

  14. Butterfield DA, Perluigi M, Sultana R (2006) Oxidative stress in Alzheimer’s disease brain: new insights from redox proteomics. Eur J Pharmacol 545:39–50

    Article  PubMed  CAS  Google Scholar 

  15. Gibbons NCJ, Wood JM, Rokos H, Schallreuter KU (2006) Computer simulation of native epidermal enzyme structures in the presence and absence of hydrogen peroxide (H2O2): potential and pitfalls. J Invest Dermatol 126:2576–2582

    Article  PubMed  CAS  Google Scholar 

  16. Whittemore ER, Loo DT, Watt JA, Cotman CW (1995) A detailed analysis of hydrogen peroxide-induced cell death in primary neuronal culture. Neuroscience 67:921–932

    Article  PubMed  CAS  Google Scholar 

  17. Parthasarathy S, Yoo B, McElheny D, Tay W, Ishii Y (2014) Capturing a reactive state of amyloid aggregates: NMR-based characterization of copper-bound Alzheimer disease amyloid β-fibrils in a redox cycle. J Biol Chem 289:9998–10010

    Article  PubMed  CAS  Google Scholar 

  18. Schallreuter KU, Elwary S (2007) Hydrogen peroxide regulates the cholinergic signal in a concentration dependent manner. Life Sci 80:2221–2226

    Article  PubMed  CAS  Google Scholar 

  19. Molochkina EM, Zorina OM, Fatkullina LD, Goloschapov AN, Burlakova EB (2005) H2O2 modifies membrane structure and activity of acetylcholinesterase. Chem-Biol Interact 157–158:401–404

    Article  PubMed  Google Scholar 

  20. Schallreuter KU, Elwary SMA, Gibbons NCJ, Rokos H, Wood JM (2004) Activation/deactivation of acetylcholinesterase by H2O2: more evidence for oxidative stress in vitiligo. Biochem Biophys Res Commun 315:502–508

    Article  PubMed  CAS  Google Scholar 

  21. Polyakov NE, Leshina TV, Konovalova TA, Kispert LD (2001) Carotenoids as scavengers of free radicals in a Fenton reaction: antioxidants or pro-oxidants? Free Radic Biol Med 31:398–404

    Article  PubMed  CAS  Google Scholar 

  22. Calderon-Garcidueñas L, Serrano-Sierra A, Torres-Jardón R, Zhu H, Yuan Y, Smith D, Delgado-Chávez R, Cross JV, Medina-Cortina H, Kavanaugh M, Guilarte TR (2013) The impact of environmental metals in young urbanites’ brains. Exp Toxicol Pathol 65:503–511

    Article  PubMed  PubMed Central  Google Scholar 

  23. Sato T, Ando Y, Susuki S, Mikami F, Ikemizu S, Nakamura M, Suhr O, Anraku M, Kai T, Suico MA, Shuto T, Mizuguchi M, Yamagata Y, Kai H (2006) Chromium(III) ion and thyroxine cooperate to stabilize the transthyretin tetramer and suppress in vitro amyloid fibril formation. FEBS Lett 580:491–496

    Article  PubMed  CAS  Google Scholar 

  24. Notarachille G, Arnesano F, Calò V, Meleleo D (2014) Heavy metals toxicity: effect of cadmium ions on amyloid beta protein 1–42. Possible implications for Alzheimer’s disease. Biometals 27:371–388

    Article  PubMed  CAS  Google Scholar 

  25. Bonting SL, Featherstone RM (1956) Ultramicro assay of the cholinesterases. Arch Biochem Biophys 61:89–98

    Article  PubMed  CAS  Google Scholar 

  26. Huang X, Atwood CS, Hartshorn MA, Multhaup G, Goldstein LE, Scarpa RC, Cuajungco MP, Gray DN, Lim J, Moir RD, Tanzi RE, Bush AI (1999) The Abeta peptide of Alzheimer’s disease directly produces hydrogen peroxide through metal ion reduction. Biochemistry 38:7609–7616

    Article  PubMed  CAS  Google Scholar 

  27. Moon MY, Kim HJ, Li Y, Kim JG, Jeon YJ, Won HY, Kim JS, Kwon HY, Choi IG, Ro E, Joe EH, Choe M, Kwon HJ, Kim HC, Kim YS, Park JB (2013) Involvement of small GTPase RhoA in the regulation of superoxide production in BV2 cells in response to fibrillar Aβ peptides. Cell Signal 25:1861–1869

    Article  PubMed  CAS  Google Scholar 

  28. Leung E, Guo L, Bu J, Maloof M, El Khoury J, Geula Ch (2011) Microglia activation mediates fibrillar amyloid-β toxicity in the aged primate cortex. Neurobiol Aging 32:387–397

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  29. Tabner BJ, El-Agnaf OMA, Turnbull S, German MJ, Paleologou KE, Hayashi Y, Cooper LJ, Fullwood NJ, Allsop D (2005) Hydrogen peroxide is generated during the very early stages of aggregation of the amyloid peptides implicated in Alzheimer disease and familial British dementia. J Biol Chem 280:35789–35792

    Article  PubMed  CAS  Google Scholar 

  30. Multhaup G, Ruppert T, Schlicksupp A, Hesse L, Beher D, Masters CL, Beyreuther K (1997) Reactive oxygen species and Alzheimer’s disease. Biochem Pharmacol 54:533–539

    Article  PubMed  CAS  Google Scholar 

  31. Baruch-Suchodolsky R, Fischer B (2008) Soluble amyloid beta1-28-copper(I)/copper(II)/iron(II) complexes are potent antioxidants in cell-free systems. Biochemistry 47:7796–7806

    Article  PubMed  CAS  Google Scholar 

  32. Vellom DC, Radić Z, Li Y, Pickering NA, Camp S, Taylor P (1993) Amino acid residues controlling acetylcholinesterase and butyrylcholinesterase specificity. Biochemistry 32:12–17

    Article  PubMed  CAS  Google Scholar 

  33. Milton NG (2004) Role of hydrogen peroxide in the aetiology of Alzheimer’s disease: implications for treatment. Drugs Aging 21:81–100

    Article  PubMed  CAS  Google Scholar 

  34. Greenough MA, Camakaris J, Bush AI (2013) Metal dyshomeostasis and oxidative stress in Alzheimer’s disease. Neurochem Int 62:540–555

    Article  PubMed  CAS  Google Scholar 

  35. Ji JA, Zhang B, Cheng W, Wang JY (2009) Methionine, tryptophan, and histidine oxidation in a model protein, PTH: mechanisms and stabilization. J Pharm Sci 98:4485–4500

    Article  PubMed  CAS  Google Scholar 

  36. Wells MA, Bruice TC (1977) Intramolecular catalysis of ester hydrolysis by metal complexed hydroxide ion. Acyl oxygen bond scission in Co2+ and Ni2+ carboxylic acid complexes. J Am Chem Soc 99:5341–5356

    Article  CAS  Google Scholar 

  37. Butterworth J, Eley DD, Stone GS (1953) Acetylcholine. 1. Hydrolysis by hydrogen and hydroxyl ion. Biochem J 53:30–34

    PubMed  CAS  PubMed Central  Google Scholar 

  38. Cuajungco MP, Fagét KY, Huang X, Tanzi RE, Bush AI (2000) Metal chelation as a potential therapy for Alzheimer’s disease. Ann N Y Acad Sci 920:292–304

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors wish to thank CONACYT (132353; 84119), CYTED: 20140482, ICyTDF (2011/276/279), and COFAA-SIP/IPN (2014/0252/1140/1115/) for their financial support.

Conflict of interest

The authors declare that no having conflicts of interest.

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Authors and Affiliations

  1. Departamento de Física, Escuela Superior de Física y Matemáticas, Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional s/n, 07738, San Pedro Zacatenco, Distrito Federal, Mexico

    Armando Méndez-Garrido, Rafael Zamorano-Ulloa & Daniel Ramírez-Rosales

  2. Laboratorio de Biofísica y Biocatálisis, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340, Casco de Santo Tomás, Distrito Federal, Mexico

    Maricarmen Hernández-Rodríguez, Jessica Elena Mendieta-Wejebe & Martha Cecilia Rosales-Hernández

  3. Laboratorio de Modelado Molecular y Diseño de Fármacos, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340, Casco de Santo Tomás, Distrito Federal, Mexico

    José Correa-Basurto

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  1. Armando Méndez-Garrido
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  7. Martha Cecilia Rosales-Hernández
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Correspondence to Martha Cecilia Rosales-Hernández.

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Méndez-Garrido, A., Hernández-Rodríguez, M., Zamorano-Ulloa, R. et al. In Vitro Effect of H2O2, Some Transition Metals and Hydroxyl Radical Produced Via Fenton and Fenton-Like Reactions, on the Catalytic Activity of AChE and the Hydrolysis of ACh. Neurochem Res 39, 2093–2104 (2014). https://doi.org/10.1007/s11064-014-1400-5

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  • DOI: https://doi.org/10.1007/s11064-014-1400-5

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