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Comparable Attenuation of Aβ25–35-Induced Neurotoxicity by Quercitrin and 17β-Estradiol in Cultured Rat Hippocampal Neurons

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Abstract

In the present work, potential protective effects of quercitrin (a phytoestrogen) on Aβ-induced neurotoxicity in cultured rat hippocampal neurons were investigated in comparison with 17β-estradiol. Cell viability, oxidative status, and antioxidative potentials were used as comparative parameters. Co-exposure of cultured neurons to Aβ25–35 with either quercitrin or 17β-estradiol (50–100 μM) for 72 h attenuated Aβ25–35-induced neurotoxicity and lipid peroxidation, but not Aβ25–35-induced ROS accumulation. However, only 17β-estradiol counteracted a reduction in glutathione content and only quercitrin counteracted a reduction in glutathione peroxidase activity. Both compounds displayed no effects on superoxide dismutase activity. A specific estrogen receptor antagonist, ICI 182780, did not abolish neuroprotective effects of quercitrin and 17β-estradiol. These findings suggested that quercitrin and 17β-estradiol attenuated Aβ25–35-induced neurotoxicity in a comparable manner. Underlying neuroprotective mechanisms of both compounds were probably not related to estrogen receptor-mediated genomic mechanisms but might involve with their antioxidant and free radical scavenging properties.

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References

  1. Selkoe DJ, Schenk D (2003) Alzheimer’s disease: molecular understanding predicts amyloid-based therapeutics. Annu Rev Pharmacol Toxicol 43:545–584

    Article  CAS  PubMed  Google Scholar 

  2. Kar S, Slowikowski SPM, Westaway D et al (2004) Interactions between β-amyloid and central cholinergic neurons: implications for Alzheimer’s disease. J Psychiatr Neurosci 29:427–441

    Google Scholar 

  3. Khan AA, Mao XO, Banwait S et al (2007) Neuroglobin attenuates β-amyloid neurotoxicity in vitro and transgenic Alzheimer phenotype in vivo. Proc Natl Acad Sci USA 104:19114–19119

    Article  CAS  PubMed  Google Scholar 

  4. Frozza RL, Horn AP, Hoppe JB et al (2009) A comparative study of β-amyloid peptides Aβ1–42 and Aβ25–35 toxicity in organotypic hippocampal slice cultures. Neurochem Res 34:295–303

    Article  CAS  PubMed  Google Scholar 

  5. Lesné S, Koh MT, Kotilinek L et al (2006) A specific amyloid-β protein assembly in the brain impairs memory. Nature 440:352–357

    Article  PubMed  Google Scholar 

  6. Jang J-H, Surh Y-J (2005) β-Amyloid-induced apoptosis is associated with cyclooxygenase-2 up-regulation via the mitogen activated protein kinase-NFκB signaling pathway. Free Radic Biol Med 38:1604–1613

    Article  CAS  PubMed  Google Scholar 

  7. Abe K, Saito H (2000) Amyloid β neurotoxicity not mediated the mitogen-activated protein kinase cascade in cultured rat hippocampal and cortical neurons. Neurosci Lett 292:1–4

    Article  CAS  PubMed  Google Scholar 

  8. Kosuge Y, Koen Y, Ishige K et al (2003) S-allyl-l-cysteine selectively protects cultured rat hippocampal neurons from amyloid β-protein- and tunicamycin-induced neuronal death. Neuroscience 122:885–895

    Article  CAS  PubMed  Google Scholar 

  9. Korol TY, Korol SV, Kostyuk EP et al (2008) β-Amyloid-induced changes in calcium homeostasis in cultured hippocampal neurons of the rat. Neurophysiology 40:9–12

    Article  Google Scholar 

  10. Xiao XQ, Wang R, Han YF et al (2000) Protective effects of huperzine A on β-amyloid25–35 induced oxidative injury in rat pheochromocytoma cells. Neurosci Lett 286:155–158

    Article  CAS  PubMed  Google Scholar 

  11. Kim H, Bang OY, Jung MW et al (2001) Neuroprotective effects of estrogen against beta-amyloid toxicity are mediated by estrogen receptors in cultured neuronal cells. Neurosci Lett 302:58–62

    Article  CAS  PubMed  Google Scholar 

  12. Keelan J, Allen NJ, Antcliffe D et al (2001) Quantitative imaging of glutathione in hippocampal neurons and glia in culture using monochlorobimane. J Neurosci Res 66:873–884

    Article  CAS  PubMed  Google Scholar 

  13. Jayakumar R, Murali J, Koteeswari D et al (2004) Cytotoxic and membrane perturbation effects of a novel amyloid forming model peptide poly (leucine-glutamic acid). J Biochem 136:457–462

    Article  CAS  PubMed  Google Scholar 

  14. Dong YL, Zuo PP, Li Q et al (2007) Protective effects of phytoestrogen α-zearalanol on beta amyloid25–35 induced oxidative damage in cultured rat hippocampal neurons. Endocrinology 32:206–211

    CAS  Google Scholar 

  15. Dhitavat S, Orti D, Rogers E et al (2005) Folate, vitamin E, and acetyl-l-carnitine provide synergistic protection against oxidative stress resulting from exposure of human neuroblastoma cells to amyloid-beta. Brain Res 1061:114–117

    Article  CAS  PubMed  Google Scholar 

  16. Nilsen J, Chen S, Irwin RW et al (2006) Estrogen protects neuronal cells from amyloid beta-induced apoptosis via regulation of mitochondrial proteins and function. BMC Neurosci 7:74–87

    Article  PubMed  Google Scholar 

  17. Roth A, Schaffner W, Hertel C (1999) Phytoestrogen kaempferol (3, 4′, 5, 7-tetrahydroxyflavone) protects PC12 and T47D cells from beta-amyloid-induced toxicity. J Neurosci Res 57:399–404

    Article  CAS  PubMed  Google Scholar 

  18. Wang CN, Chi CW, Lin YL et al (2001) The neuroprotective effects of phytoestrogens on amyloid β protein-induced toxicity are mediated by abrogating the activation of caspase cascade in rat cortical neurons. J Biol Chem 276:5287–5295

    Article  CAS  PubMed  Google Scholar 

  19. Zeng H, Chen Q, Zhao B (2004) Genistein ameliorates β-amyloid peptide (25–35)-induced hippocampal neuronal apoptosis. Free Radic Biol Med 36:180–188

    Article  CAS  PubMed  Google Scholar 

  20. Bang OY, Hong HS, Kim DH et al (2004) Neuroprotective effect of genistein against beta amyloid-induced neurotoxicity. Neurobiol Dis 16:21–28

    Article  CAS  PubMed  Google Scholar 

  21. Wagner C, Fachinetto R, Dalla Corte CL et al (2006) Quercitrin, a glycoside form of quercetin, prevents lipid peroxidation in vitro. Brain Res 1107:192–198

    Article  CAS  PubMed  Google Scholar 

  22. Kraus B, Wolff H, Heilmann J et al (2007) Influence of Hypericum perforatum extract and its single compounds on amyloid-β mediated toxicity in microglial cells. Life Sci 81:884–894

    Article  CAS  PubMed  Google Scholar 

  23. Hollman PC, de Vries JH, Van Leeuwen SD et al (1995) Absorption of dietary quercetin glycosides and quercetin in healthy ileostomy volunteers. Am J Clin Nutr 62:1276–1282

    CAS  PubMed  Google Scholar 

  24. Morand C, Manach C, Crespy V et al (2000) Quercetin 3-O-beta-glucoside is better absorbed than other quercetin forms and is not present in rat plasma. Free Radic Res 33:667–676

    Article  CAS  PubMed  Google Scholar 

  25. Unchern S, Nagata K, Saito H (1997) Selective cytotoxicity of piperine on cultured rat hippocampal neurons in comparison with cultured astrocytes: the possible involvement of lipid peroxidation. Biol Pharm Bull 20:958–961

    CAS  PubMed  Google Scholar 

  26. Pike C, Overman MJ, Cotman CW (1995) Amino terminal detection enhanced aggregation of beta amyloid peptide in vitro. J Biol Chem 270:23895–23898

    Article  CAS  PubMed  Google Scholar 

  27. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63

    Article  CAS  PubMed  Google Scholar 

  28. 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 

  29. Bastianetto S, Zheng WH, Quirion R (2000) The Ginkgo biloba extract (EGb 761) protects hippocampal neurons against cell death induced by beta-amyloid. Eur J Neurosci 12:1882–1890

    Article  CAS  PubMed  Google Scholar 

  30. Tietze F (1969) Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal Biochem 27:502–522

    Article  CAS  PubMed  Google Scholar 

  31. 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 

  32. Jiang X, Mu D, Manabat C et al (2004) Differential vulnerability of immature murine neurons to oxygen-glucose deprivation. Exp Neurol 190:224–232

    Article  CAS  PubMed  Google Scholar 

  33. Shirai K, Mizui T, Suzuki Y et al (2006) Differential effects of x-irradiation on immature and mature hippocampal neurons in vitro. Neurosci Lett 399:57–60

    Article  CAS  PubMed  Google Scholar 

  34. Behl C, Skutella T, Lezoualch F et al (1997) Neuroprotection against oxidative stress by estrogens: structure–activity relationship. Mol Pharmacol 51:535–541

    CAS  PubMed  Google Scholar 

  35. Yagyu K, Kitagawa K, Irie T et al (2001) Amyloid proteins inhibit Cl–ATPase activity in cultured rat hippocampal neurons. J Neurochem 78:569–576

    Article  CAS  PubMed  Google Scholar 

  36. Fitzpatrick JL, Mize AL, Wade CB et al (2002) Estrogen-mediated neuroprotection against beta-amyloid toxicity requires expression of estrogen receptor alpha or beta and activation of MAPK pathway. J Neurochem 82:674–682

    Article  CAS  PubMed  Google Scholar 

  37. Quintanilla RA, Muñoz FJ, Metcalfe MJ et al (2005) Trolox and 17β-estradiol protect against amyloid β-peptide neurotoxicity by a mechanism that involves modulation of the Wnt signaling pathway. J Biol Chem 280:11615–11625

    Article  CAS  PubMed  Google Scholar 

  38. Canevari L, Abramov AY, Duchen MR (2004) Toxicity of amyloid β peptide: tales of calcium, mitochondria, and oxidative stress. Neurochem Res 29:637–650

    Article  CAS  PubMed  Google Scholar 

  39. Benzi G, Moretti A (1995) Are reactive oxygen species involved in Alzheimer’s disease? Neurobiol Aging 16:661–674

    Article  CAS  PubMed  Google Scholar 

  40. Lovell MA, Ehmann WD, Butler SM et al (1995) Elevated thiobarbituric acid-reactive substances and antioxidant enzyme activity in the brain in Alzheimer’s disease. Neurology 45:1594–1601

    CAS  PubMed  Google Scholar 

  41. Marcus DL, Thomas C, Rodriguez C et al (1998) Increased peroxidation and reduced antioxidant enzyme activity in Alzheimer’s disease. Exp Neurol 150:40–44

    Article  CAS  PubMed  Google Scholar 

  42. Butterfield DA, Lauderback CM (2002) Lipid peroxidation and protein oxidation in Alzheimer’s disease brain: potential causes and consequences involving amyloid β-peptide-associated free radical oxidative stress. Free Radic Bio Med 32:1050–1060

    Article  CAS  Google Scholar 

  43. Bae YH, Hwang JY, Kim YH et al (2000) Antioxidative neuroprotection by estrogens in mouse cortical cultures. J Korean Med Sci 15:327–336

    CAS  PubMed  Google Scholar 

  44. Cecchi C, Latorraca S, Sorbi S et al (1999) Glutathione level is altered in lymphoblasts from patients with familial Alzheimer’s disease. Neurosci Lett 275:152–154

    Article  CAS  PubMed  Google Scholar 

  45. Abramov AY, Canevari L, Duchen MR (2003) Changes in intracellular calcium and glutathione in astrocytes as the primary mechanism of amyloid neurotoxicity. J Neurosci 23:5088–5095

    CAS  PubMed  Google Scholar 

  46. Reiter RJ (1995) Oxidative processes and antioxidative defense mechanisms in the aging brain. FASEB J 9:526–533

    CAS  PubMed  Google Scholar 

  47. McEwen B (2002) Estrogen actions throughout the brain. Recent Prog Horm Res 57:357–384

    Article  CAS  PubMed  Google Scholar 

  48. Dubal DB, Shughrue PJ, Wilson ME et al (1999) Estradiol modulates bcl-2 in cerebral ischemia: a potential role for estrogen receptors. J Neurosci 19:6385–6393

    CAS  PubMed  Google Scholar 

  49. Sawada H, Ibi M, Kihara T et al (2000) Mechanisms of antiapoptotic effects of estrogens in nigral dopaminergic neurons. FASEB J 14:1202–1214

    CAS  PubMed  Google Scholar 

  50. Wilson ME, Dubal DB, Wise PM (2000) Estradiol protects against injury-induced cell death in cortical explant cultures: a role for estrogen receptors. Brain Res 873:235–242

    Article  CAS  PubMed  Google Scholar 

  51. Lee SY, Andoh T, Murphy DL et al (2003) 17β-Estradiol activates ICI 182, 780-sensitive estrogen receptors and cyclic GMP-dependent thioredoxin expression for neuroprotection. FASEB J 17:947–948

    CAS  PubMed  Google Scholar 

  52. Howard SA, Brooke SM, Sapolsky RM (2001) Mechanisms of estrogenic protection against gp 120-induced neurotoxicity. Exp Neurol 168:385–391

    Article  CAS  PubMed  Google Scholar 

  53. Wang X, Dykens JA, Perez E et al (2006) Neuroprotective effects of 17β-estradiol and nonfeminizing estrogens against H2O2 toxicity in human neuroblastoma SK-N-SH cells. Mol Pharmacol 70:395–404

    Article  CAS  PubMed  Google Scholar 

  54. Behl C, Widmann M, Trapp T et al (1995) 17-beta estradiol protects neurons from oxidative stress-induced cell death in vitro. Biochem Biophys Res Comm 216:473–482

    Article  CAS  PubMed  Google Scholar 

  55. Xu C, Bailly-Maitre B, Reed JC (2005) Endoplasmic reticulum stress: cell life and death decisions. J Clin Invest 115:2656–2664

    Article  CAS  PubMed  Google Scholar 

  56. Yoshida H (2007) ER stress and diseases. FEBS J 274:630–658

    Article  CAS  PubMed  Google Scholar 

  57. Imai T, Kosuge Y, Ishige K et al (2007) Amyloid β-protein potentiates tunicamycin-induced neuronal death in organotypic hippocampal slice cultures. Neuroscience 147:639–651

    Article  CAS  PubMed  Google Scholar 

  58. Natsume Y, Ito S, Satsu H et al (2009) Protective effect of quercetin on ER stress caused by calcium dynamics dysregulation in intestinal epithelial cells. Toxicology 258:164–175

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported partly by the Graduate Research Funds from the Graduate School, Chulalongkorn University.

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Correspondence to Surachai Unchern.

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Rattanajarasroj, S., Unchern, S. Comparable Attenuation of Aβ25–35-Induced Neurotoxicity by Quercitrin and 17β-Estradiol in Cultured Rat Hippocampal Neurons. Neurochem Res 35, 1196–1205 (2010). https://doi.org/10.1007/s11064-010-0175-6

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