Skip to main content

Advertisement

SpringerLink
Log in

Sulforaphane Prevents Methylmercury-Induced Oxidative Damage and Excitotoxicity Through Activation of the Nrf2-ARE Pathway

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Methylmercury (MeHg) is a prominent environmental neurotoxicant, which induces oxidative damage and an indirect excitotoxicity caused by altered glutamate (Glu) metabolism. However, the interaction between oxidative damage and excitotoxicity in MeHg-exposed rats has not been fully recognized. Here, we explored the interaction between oxidative damage and excitotoxicity and evaluated the preventive effects of sulforaphane (SFN) on MeHg-induced neurotoxicity in rat cerebral cortex. Seventy-two rats were randomly assigned to four groups: control group, MeHg-treated groups (4 and 12 μmol/kg), and SFN pretreatment group. After treatment (28 days), the rats were killed and the cerebral cortex was analyzed. Then, Hg, glutathione (GSH), malondialdehyde (MDA), protein sulfhydryl, protein carbonyl, 8-hydroxy-2-deoxyguanosine (8-OHdG), and the levels of reactive oxygen species (ROS) and apoptosis were examined. Glu and glutamine (Gln) levels, glutamine synthetase (GS), phosphate-activated glutaminase (PAG), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), Na+-K+-ATPase and Ca2+-ATPase activities, intracellular Ca2+ levels, and the mRNA and protein expressions of Nrf2, Nrf2-regulated gene products, and N-methyl-d-aspartate receptors (NMDARs) were investigated in rat cerebral cortex. In our study, MeHg exposure not only induced Hg accumulation, apoptosis, ROS formation, GSH depletion, inhibition of antioxidant enzyme activities, and activation of Nrf2-ARE pathway signaling but also caused lipid, protein, and DNA peroxidative damage in a dose-dependent manner in rat cerebral cortex. Moreover, MeHg treatment significantly altered Gln/Glu cycling and NMDAR expression and resulted in calcium overloading. Furthermore, the present study also indicated that SFN pretreatment significantly reinforced the activation of the Nrf2-ARE pathway, which could prevent the toxic effects of MeHg exposure. Collectively, MeHg initiates multiple additive or synergistic disruptive mechanisms that lead to oxidative damage and excitotoxicity in rat cerebral cortex; pretreatment with SFN might prevent the MeHg-induced neurotoxicity by reinforcing the activation of the Nrf2-ARE pathway and then downregulating the interaction between oxidative damage and excitotoxicity pathways.

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
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Clarkson TW, Magos L, Myers GJ (2003) Current concepts: the toxicology of mercury—current exposures and clinical manifestations. N Engl J Med 349(18):1731–1737. doi:10.1056/NEJMra022471

    Article  CAS  PubMed  Google Scholar 

  2. Manfroi CB, Schwalm FD, Cereser V, Abren F, Oliveira A, Bizarro L, Rocha JBT, Frizzo MES et al (2004) Maternal milk as methylmercury source for suckling mice: neurotoxic effects involved with the cerebellar glutamatergic system. Toxicol Sci 81(1):172–178. doi:10.1093/toxsci/kfh201

    Article  CAS  PubMed  Google Scholar 

  3. Yin Z, Milatovic D, Aschner JL, Syversen T, Rocha JBT, Souza DO, Sidoryk M, Albrecht J et al (2007) Methylmercury induces oxidative injury, alterations in permeability and glutamine transport in cultured astrocytes. Brain Res 1131(1):1–10. doi:10.1016/j.brainres.2006.10.070

    Article  CAS  PubMed  Google Scholar 

  4. Aschner M, Yao CP, Allen JW, Tan KH (2000) Methylmercury alters glutamate transport in astrocytes. Neurochem Int 37(2–3):199–206. doi:10.1016/S0197-0186(00)00023-1

    Article  CAS  PubMed  Google Scholar 

  5. Farina M, Dahm KC, Schwalm FD, Brusque AM, Frizzo ME, Zeni G, Souza DO, Rocha JB (2003) Methylmercury increases glutamate release from brain synaptosomes and glutamate uptake by cortical slices from suckling rat pups: modulatory effect of ebselen. Toxicol Sci 73:135–140. doi:10.1093/toxsci/kfg058

    Article  CAS  PubMed  Google Scholar 

  6. Mutkus L, Aschner JL, Syversen T, Aschner M (2005) Methylmercury alters the in vitro uptake of glutamate in GLAST- and GLT-1-transfected mutant CHO-K1 cells. Biol Trace Elem Res 107(3):231–245. doi:10.1385/BTER:107:3:231

    Article  CAS  PubMed  Google Scholar 

  7. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39(1):44–84. doi:10.1016/j.biocel.2006.07.001

    Article  CAS  PubMed  Google Scholar 

  8. Castoldi AF, Coccini T, Ceccatelli S, Manzo L (2001) Neurotoxicity and molecular effects of methylmercury. Brain Res Bull 55(2):197–203. doi:10.1016/S0361-9230(01)00458-0

    Article  CAS  PubMed  Google Scholar 

  9. Johansson C, Castoldi AF, Onishchenko N, Manzo L, Vahter M, Ceccatelli S (2007) Neurobehavioural and molecular changes induced by methylmercury exposure during development. Neurotox Res 11(3–4):241–260. doi:10.1007/BF03033570

    Article  CAS  PubMed  Google Scholar 

  10. Kaur P, Schulz K, Heggland I, Aschner M, Syversen T (2008) The use of fluorescence for detecting MeHg-induced ROS in cell cultures. Toxicol In Vitro 22(5):1392–1398. doi:10.1016/j.tiv.2008.01.01

    Article  CAS  PubMed  Google Scholar 

  11. Stringari J, Nunes AKC, Franco JL, Bohrer D, Garcia SC, Dafre AL, Milatovic D, Souza DO et al (2008) Prenatal methylmercury exposure hampers glutathione antioxidant system ontogenesis and causes long-lasting oxidative stress in the mouse brain. Toxicol Appl Pharmacol 227(1):147–154. doi:10.1016/j.taap.2007.10.010

    Article  CAS  PubMed  Google Scholar 

  12. Dreiem A, Seegal RF (2007) Methylmercury-induced changes in mitochondrial function in striatal synaptosomes are calcium-dependent and ROS-independent. NeuroToxicology 28(4):720–726. doi:10.1016/j.neuro.2007.03.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Alko M, Morris H, Cronin M (2005) Metals, toxicity and oxidative stress. Curr Med Chem 12(10):1161–1208. doi:10.2174/0929867053764635

    Article  Google Scholar 

  14. Qiuyin C, Rahn RO, Ruiwen Z (1997) Dietary flavonoids, quercetin, luteolin and genistein, reduce oxidative DNA damage and lipid peroxidation and quench free radicals. Cancer Lett 119(1):99–107. doi:10.1016/S0304-3835(97)00261-9

    Article  Google Scholar 

  15. Franco JL, Braga HC, Stringari J (2007) Mercurial-induced hydrogen peroxide generation in mouse brain mitochondria: protective effects of quercetin. Chem Res Toxicol 20(12):1919–1926. doi:10.1021/tx7002323

    Article  CAS  PubMed  Google Scholar 

  16. Lucena GM, Franco JL, Ribas CM, Azevedo MS, Meotti FS, Gadotti VM (2007) Cipura paludosa extract prevents methyl mercury-induced neurotoxicity in mice. Basic Clin Pharmacol Toxicol 101(2):127–131. doi:10.1111/j.1742-7843.2007.00091.x

    Article  CAS  PubMed  Google Scholar 

  17. Farina M, Campos F, Vendrell I, Berenguer J, Barzi M, Pons S, Surrol C (2009) Probucol increases glutathione peroxidase-1 activity and displays long-lasting protection against methylmercury toxicity in cerebellar granule cells. Toxicol Sci 112(2):416–426. doi:10.1093/toxsci/kfp219

    Article  CAS  PubMed  Google Scholar 

  18. Farina M, Soares FA, Zeni G, Souza DO, Rocha JBT (2004) Additive pro-oxidative effects of methylmercury and ebselen in liver from suckling rat pups. Toxicol Lett 146(3):227–235. doi:10.1016/j.toxlet.2003.10.001

    Article  CAS  PubMed  Google Scholar 

  19. Chang JY, Tsai PF (2008) Prevention of methylmercury-induced mitochondrial depolarization, glutathione depletion and cell death by 15-deoxy-delta-12, 14-prostaglandin J(2). NeuroToxicology 29(6):1054–1061. doi:10.1016/j.neuro.2008.08.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Roos DH, Puntel RL, Santos MM, Souza DO, Farina M, Nogueira CW, Aschner M, Burger ME et al (2009) Guanosine and synthetic organoselenium compounds modulate methylmercury-induced oxidative stress in rat brain cortical slices: involvement of oxidative stress and glutamatergic system. Toxicol in Vitro 23(2):302–307. doi:10.1016/j.tiv.2008.12.020

    Article  CAS  PubMed  Google Scholar 

  21. Nguyen T, Sherratt PJ, Pickett CB (2003) Regulatory mechanisms controlling gene expression mediated by the antioxidant response element. Annu Rev Pharmacol Toxicol 43:233–260. doi:10.1146/annurev.pharmtox.43.100901.140229

    Article  CAS  PubMed  Google Scholar 

  22. Itoh K, Tong KI, Yamamoto M (2004) Molecular mechanism activating Nrf2-Keap1 pathway in regulation of adaptive response to electrophiles. Free Radic Biol Med 36(10):1208–1213. doi:10.1016/j.freeradbiomed.2004.02.075

    Article  CAS  PubMed  Google Scholar 

  23. Motohashi H, Yamamoto M (2004) Nrf2-Keap1 defines a physiologically important stress response mechanism. Trends Mol Med 10(11):549–557. doi:10.1016/j.molmed.2004.09.003

    Article  CAS  PubMed  Google Scholar 

  24. Kensler TW, Wakabayashi N, Biswal S (2007) Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol 47:89–116. doi:10.1146/annurev.pharmtox.46.120604.141046

    Article  CAS  PubMed  Google Scholar 

  25. Kobayashi M, Yamamoto M (2006) Nrf2-Keap1 regulation of cellular defense mechanisms against electrophiles and reactive oxygen species. Adv Enzym Regul 46(1):113–140. doi:10.1016/j.advenzreg.2006.01.007

    Article  CAS  Google Scholar 

  26. Jyrkkänen HK, Kuosmanen S, Heinäniemi M, Laitinen H, Kansanen E, Mella-Aho E (2011) Novel insights into the regulation of antioxidant-response-element-mediated gene expression by electrophiles: induction of the transcriptional repressor BACH1 by Nrf2. Biochem J 440(2):167–174. doi:10.1042/BJ20110526

    Article  PubMed  Google Scholar 

  27. Lau A, Tymianski M (2010) Glutamate receptors, neurotoxicity and neurodegeneration. Pflugers Arch - Eur J Physiol 460(2):525–542. doi:10.1007/s00424-010-0809-1

    Article  CAS  Google Scholar 

  28. LiuY WTP, Aarts M, Rooyakkers A, Liu L, Lai TW (2007) NMDA receptor subunits have differential roles immediating excitotoxic neuronal death both in vitro and in vivo. J Neurosci 27(11):2846–2857. doi:10.1523/JNEUROSCI.0116-07.2007

    Article  Google Scholar 

  29. Juárez BI, Martínez ML, Montante M, Dufour L, Garcıa E, Jimenez-Capdeville ME (2002) Methylmercury increases glutamate extracellular levels in frontal cortex of awake rats. Neurotoxicol Teratol 24(6):767–771. doi:10.1016/S0892-0362(02)00270-2

    Article  PubMed  Google Scholar 

  30. Juge N, Mithen RF, Traka M (2007) Molecular basis for chemoprevention by sulforaphane: a comprehensive review. Cell Mol Life Sci 64(9):1105–1127. doi:10.1007/s00018-007-6484-5

    Article  CAS  PubMed  Google Scholar 

  31. Negrette-Guzmán M, Huerta-Yepez S, Medina-Campos ON, Zatarain-Barrón H-PR, Torres I, Tapia E, Pedraza-Chaverri J (2013) Sulforaphane attenuates gentamicin-induced nephrotoxicity: role of mitochondrial protection. Evid Based Complement Alternat Med 2013:135314. doi:10.1155/2013/135314

    Article  PubMed  PubMed Central  Google Scholar 

  32. Negrette-Guzmán M, Huerta-Yepez S, Tapia E, Pedraza-Chaverri J (2013) Modulation of mitochondrial functions by the indirect antioxidant sulforaphane: a seemingly contradictory dual role and an integrative hypothesis. Free Radic Biol Med 65:1078–1089. doi:10.1016/j.freeradbiomed.2013.08.182

    Article  PubMed  Google Scholar 

  33. Kraft AD, Johnson DA, Johnson JA (2004) Nuclear factor E2-related factor 2-dependent antioxidant response element activation by tertbutylhydroquinone and sulforaphane occurring preferentially in astrocytes conditions neuron against oxidative insult. J Neurosci 24(5):1101–1112. doi:10.1523/JNEUROSCI.3817-03.2004

    Article  CAS  PubMed  Google Scholar 

  34. King MD, Lindsay DS, Holladay S, Ehrich M (2003) Neurotoxicity and immunotoxicity assessment in CBA/J mice with chronic Toxoplasma gondii infection and multiple oral exposures to methylmercury. J Parasitol 89(4):856–859. doi:10.1645/GE-79R

    Article  CAS  PubMed  Google Scholar 

  35. Nakamura M, Yasutake A, Fujimura M, Hachiya N, Marumoto M (2011) Effects of methylmercury administration on choroid plexus function in rats. Arch Toxicol 85(8):911–918. doi:10.1007/s00204-010-0623-8

    Article  CAS  PubMed  Google Scholar 

  36. Toyama T, Shinkai Y, Yasutake A, Uchida K, Yamamoyo M, Kumagai Y (2011) Isothiocyanates reduce mercury accumulation via an Nrf2-dependent mechanism during exposure of mice to mercury. Environ Health Perspect 119(8):1117–1122. doi:10.1289/ehp.1003123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Xu B, Xu ZF, Deng Y (2010) Manganese exposure alters the expression of N-methyl-D-aspartate receptor subunit mRNAs and proteins in rat striatum. J Biochem Mol Toxicol 24(1):1–9. doi:10.1002/jbt.20306

    Article  PubMed  Google Scholar 

  38. Stockwell PB, Corns WT (1993) The role of atomic fluorescence spectrometry in the automatic environmental monitoring of trace element analysis. J Automat Chem 15(3):79–84. doi:10.1155/S1463924693000136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Cheng WW, Lin ZQ, Wei BF, Zeng Q, Han B, Wei CX (2011) Single-walled carbon nanotube induction of rat aortic endothelial cell apoptosis: reactive oxygen species are involved in the mitochondrial pathway. Int J Biochem Cell Biol 43(4):564–572. doi:10.1016/j.biocel.2010.12.013

    Article  CAS  PubMed  Google Scholar 

  40. Ahamed M, Akhtar MJ, Siddiqui MA, Ahmad J, Musarrat J, AI-Khedhairy AA (2011) Oxidative stress mediated apoptosis induced by nickel ferrite nanoparticles in cultured A549 cells. Toxicology 283(2–3):101–108. doi:10.1016/j.tox.2011.02.010

    Article  CAS  PubMed  Google Scholar 

  41. Mori N, Yasutake A, Hirayama K (2007) Comparative study of activities in reactive oxygen species production/defense system in mitochondria of rat brain and liver, and their susceptibility to methylmercury toxicity. Arch Toxicol 81(11):769–776. doi:10.1007/s00204-007-0209-2

    Article  CAS  PubMed  Google Scholar 

  42. Allen JW, Shanker G, Aschner M (2001) Methylmercury inhibits the in vitro uptake of the glutathione precursor, cystine, in astrocytes, but not in neurons. Brain Res 894(1):131–140. doi:10.1016/S0006-8993(01)01988-6

    Article  CAS  PubMed  Google Scholar 

  43. Kenny J, Bao Y, Hamm B, Taylor L, Toth A, Wagers B, Curthoys NP (2003) Bacterial expression, purification, and characterization of rat kidney-type mitochondrial glutaminase. Protein Expr Purif 31(1):140–148. doi:10.1016/S1046-5928(03)00161-X

    Article  CAS  PubMed  Google Scholar 

  44. Paredes-Gamero EJ, Franca JP, Moraes AAFS, Aguilar MO, Oshiro MEM, Ferreira AT (2004) Problems caused by high concentration of ATP on activation of the P2X7 receptor in bone marrow cells loaded with the Ca2+ fluorophore fura-2. Exp Brain Res 108(3):357–366. doi:10.1023/B:JOFL.0000047221.51493.e3

    Google Scholar 

  45. Murali G, Panneerselvam KS, Panneerselvam C (2008) Age-associated alterations of lipofuscin, membrane-bound ATPases and intracellular calcium in cortex, striatum and hippocampus of rat brain: protective role of glutathione monoester. Int J Dev Neurosci 26(2):211–215. doi:10.1016/j.ijdevneu.2007.12.004

    Article  CAS  PubMed  Google Scholar 

  46. Yin Z, Jiang H, Syversen T, Rocha JB, Farina M, Aschner M (2008) The methylmercury-L-cysteine conjugate is a substrate for the L-type large neutral amino acid transporter. J Neurochem 107(4):1083–1090. doi:10.1111/j.1471-4159.2008.05683.x

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Roos DH, Puntel RL, Lugokenski TH, Ineu RP, Bohrer D, Burger ME (2010) Complex methylmercury-cysteine alters mercury accumulation in different tissues of mice. Basic Clin Pharmacol Toxicol 107(4):789–792. doi:10.1111/j.1742-7843.2010.00577.x

    Article  CAS  PubMed  Google Scholar 

  48. Nel A, Xia T, Mädler L, Ning L (2006) Toxic potential of materials at the nanolevel. Science 311(5761):622–627. doi:10.1126/science.1114397

    Article  CAS  PubMed  Google Scholar 

  49. Stone V, Donaldson K (2006) Nanotoxicology: signs of stress. Nat Nanotech 1(1):23–24. doi:10.1038/nnano.2006.69

    Article  CAS  Google Scholar 

  50. Gegg M, Beltran B, Salas-Pino S, Bolaŕíos JP, Clark JB, Moncada S (2003) Differential effect of nitric oxide on GSH metabolism and mitochondrial function in astrocytes and neurons: implications for neuroprotection/neurodegeneration. J Neurochem 86(1):228–237. doi:10.1046/j.1471-4159.2003.01821.x

    Article  CAS  PubMed  Google Scholar 

  51. Franco JL, Posser T, Dunkley PR, Dickson PW, Mattos JJ, Martins R, Bainy AC, Marques MR et al (2009) Methylmercury neurotoxicity is associated with inhibition of the antioxidant enzyme glutathione peroxidase. Free Radic Biol Med 47(4):449–457. doi:10.1016/j.freeradbiomed.2009.05.013

    Article  CAS  PubMed  Google Scholar 

  52. Niki E, Yoshida Y, Saito Y, Noquchi N (2005) Lipid peroxidation: mechanisms, inhibition, and biological effects. Biochem Biophys Res Commun 338(1):668–676. doi:10.1016/j.bbrc.2005.08.072

    Article  CAS  PubMed  Google Scholar 

  53. Alturfan AA, Tozan-Beceren A, Sehirli AÖ, Demiralp E, Sener G, Omurtag GZ (2012) Resveratrol ameliorates oxidative DNA damage and protects against acrylamide-induced oxidative stress in rats. Mol Biol Rep 39(4):4589–4596. doi:10.1007/s11033-011-1249-5

    Article  CAS  PubMed  Google Scholar 

  54. Carvalho MC, Franco JL, Ghizoni H, Kobus-Bianchini K, Nazari E, Joäo B (2007) Effects of 2,3-dimercapto-1-propanesulfonic acid (DMPS) on methylmercury-induced locomotor deficits and cerebellar toxicity in mice. Toxicology 239(3):195–203. doi:10.1016/j.tox.2007.07.009

    Article  CAS  PubMed  Google Scholar 

  55. Ni M, Li X, Yin Z, Jiang H, Sidoryk-Wegrzynowicz M, Milatovic D (2010) Methylmercury induces acute oxidative stress, altering Nrf2 protein level in primary microglial cells. Toxicol Sci 116(2):590–603. doi:10.1093/toxsci/kfq126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Zhang DD, Hannink M (2003) Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. Mol Cell Biol 23(22):8137–8151. doi:10.1128/MCB.23.22.8137-8151.2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Hazell AS (2007) Excitotoxic mechanisms in stroke: an update of concepts and treatment strategies. Neurochem Int 50(7–8):941–953. doi:10.1016/j.neuint.2007.04.026

    Article  CAS  PubMed  Google Scholar 

  58. Boulland JL, Osen KK, Levy LM, Danbolt NC, Edwards RH, Storm-Mathisen J (2002) Cell-specific expression of the glutamine transporter SN1 suggests differences in dependence on the glutamine cycle. Eur J Neurosci 15(10):1615–1631. doi:10.1046/j.1460-9568.2002.01995.x

    Article  PubMed  Google Scholar 

  59. Sidoryk-Wegrzynowicz M, Lee E, Albrecht J, Aschner M (2009) Manganese disrupts astrocyte glutamine transporter expression and function. J Neurochem 110(3):822–830. doi:10.1111/j.1471-4159.2009.06172.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Xu B, Xu ZF, Deng Y (2010) Protective effects of MK-801 on manganese-induced glutamate metabolism disorder in rat striatum. Exp Toxicol Pathol 62(4):381–390. doi:10.1016/j.etp.2009.05.007

    Article  CAS  PubMed  Google Scholar 

  61. Ahmed I, Bose SK, Pavese N, Ramlackhansingh A, Turkheimer F, Hotton G, Hammers A, Brooks DJ (2011) Glutamate NMDA receptor dysregulation in Parkinson’s disease with dyskinesias. Brain 134(Pt4):979–986. doi:10.1093/brain/awr028

    Article  PubMed  Google Scholar 

  62. Nakamichi N, Yoneda Y (2006) Maturation-dependent reduced responsiveness of intracellular free Ca2+ ions to repeated stimulation by N-methyl-D-aspartate in cultured rat cortical neurons. Neurochem Int 49(3):230–237. doi:10.1016/j.neuint.2006.01.010

    Article  CAS  PubMed  Google Scholar 

  63. Jantas D, Lason W (2009) Different mechanisms of NMDA-mediated protection against neuronal apoptosis: a stimuli-dependent effect. Neurochem Res 34(11):2040–2054. doi:10.1007/s11064-009-9991-y

    Article  CAS  PubMed  Google Scholar 

  64. Allgaier C (2002) Ethanol sensitivity of NMDA receptors. Neuroche Int 41(6):377–382. doi:10.1016/S0197-0186(02)00046-3

    Article  CAS  Google Scholar 

  65. Nakamichi N, Ohno H, Kuramoto N, Yoneda Y (2002) Dual mechanisms of Ca (2+) increases elicited by N-methyl-D-aspartate in immature and mature cultured cortical neurons. J Neurosci Res 67(2):275–283. doi:10.1002/jnr.10096

    Article  CAS  PubMed  Google Scholar 

  66. Sanz-Blasco S, Valero RA, Rodriguez-Crespo I, Villalobos C, Nunez L (2008) Mitochondrial Ca2+ overload underlies Abeta oligomers neurotoxicity providing an unexpected mechanism of neuroprotection by NSAIDs. PLoS One 3(7):e2718. doi:10.1371/journal.pone.0002718

    Article  PubMed  PubMed Central  Google Scholar 

  67. Swamy M, Salleh MJM, Sirajudeen KNS, Yusof WRW, Chandran G (2010) Nitric oxide (no), citrulline - no cycle enzymes, glutamine synthetase and oxidative stress in anoxia (hypobaric hypoxia) and reperfusion in rat brain. Int J Med Sci 7(3):147–154. doi:10.1080/01480540903130641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Liu CH, Jiao H, Guo ZH, Peng Y, Wang WZ (2013) Up-regulated GLT-1 resists glutamate toxicity and attenuates glutamate-induced calcium loading on cultured neurocytes. Basic Clin Pharmacol Toxicol 112(1):19–24. doi:10.1111/bcpt.12011

    Article  CAS  PubMed  Google Scholar 

  69. He Y, Cui J, Lee JC, Ding S, Chalimoniuk M, Simonvi A, Sun AY, Gu Z et al (2011) Prolonged exposure of cortical neurons to oligomeric amyloid-β impairs NMDA receptor function via NADPH oxidase-mediated ROS production: protective effect of green tea (−)-epigallocatechin-3-gallate. ASN Neuro 3(1):e00050. doi:10.1042/AN20100025

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (No. 81172631).

Author information

Authors and Affiliations

  1. Department of Environmental Health, School of Public Health, China Medical University, Shenyang, 110122, Liaoning Province, People’s Republic of China

    Shu Feng, Zhaofa Xu, Fei Wang, Tianyao Yang, Wei Liu, Yu Deng & Bin Xu

Authors
  1. Shu Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhaofa Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tianyao Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wei Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yu Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bin Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhaofa Xu.

Ethics declarations

Conflict of Interest

The authors declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Feng, S., Xu, Z., Wang, F. et al. Sulforaphane Prevents Methylmercury-Induced Oxidative Damage and Excitotoxicity Through Activation of the Nrf2-ARE Pathway. Mol Neurobiol 54, 375–391 (2017). https://doi.org/10.1007/s12035-015-9643-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-015-9643-y

Keywords

Search

Navigation