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17β-Estradiol Delays 6-OHDA-Induced Apoptosis by Acting on Nur77 Translocation from the Nucleus to the Cytoplasm

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Abstract

Nuclear receptors (Nurs) represent a large family of gene expression regulating proteins. Gathering evidence indicates an important role for Nurs as transcription factors in dopamine neurotransmission. Nur77, a member of the Nur superfamily, plays a role in mediating the effects of antiparkinsonian and neuroleptic drugs. Besides, Nur77 survival and apoptotic roles depend largely on its subcellular localization. Estrogens are known for their neuroprotective properties, as demonstrated in animal and clinical studies. However, their action on Nur77 translocation pertaining to neuroprotection has not been investigated yet. The aim of our study was to perform a kinetic study on the effect of neurotoxic 6-hydroxydopamine (6-OHDA) and 17β-estradiol (E2) on the subcellular localization of Nur77 with reference to the modulation of apoptosis in PC12 cells. Our results demonstrate that E2 administration alone does not affect Nur77 cytoplasmic/nuclear ratio, mRNA levels, or apoptosis in PC12 cells. The neurotoxin 6-OHDA significantly enhances cytoplasmic localization of Nur77 after merely 3 h, while precipitating apoptosis. 6-OHDA also increases Nur77 transcription, which could partly explain the rise in cytoplasmic localization of the protein. Finally, treatment with both E2 and 6-OHDA delays Nur77 accumulation in the cytoplasm and delays cell death for a few hours in our cellular paradigm. Pre-treatment with E2 does not alter the increase in levels of Nur77 mRNA produced by 6-OHDA, suggesting that a raise in nuclear translocation is likely responsible for the stabilization of the cytoplasmic/nuclear ratio until 6 h. These results suggest an intriguing cooperation between E2 and Nur77 toward cellular fate guidance.

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References

  • Al Sweidi S, Sánchez MG, Bourque M, Morissette M, Dluzen D, Di Paolo T (2012) Oestrogen receptors and signalling pathways: implications for neuroprotective effects of sex steroids in Parkinson’s disease. J Neuroendocrinol 24(1):48–61

    Article  CAS  PubMed  Google Scholar 

  • Barron AM, Pike CJ (2012) Sex hormones, aging, and Alzheimer’s disease. Front Biosci (Elite Ed) 4:976–997

    Google Scholar 

  • Beaudry G, Langlois MC, Weppe I, Rouillard C, Levesque D (2000) Contrasting patterns and cellular specificity of transcriptional regulation of the nuclear receptor nerve growth factor-inducible B by haloperidol and clozapine in the rat forebrain. J Neurochem 75(4):1694–1702

    Article  CAS  PubMed  Google Scholar 

  • Boldingh Debernard KA, Mathisen GH, Paulsen RE (2012) Differences in NGFI-B, Nurr1, and NOR-1 expression and nucleocytoplasmic translocation in glutamate-treated neurons. Neurochem Int 61(1):79–88

    Article  CAS  PubMed  Google Scholar 

  • Bonta PI, van Tiel CM, Vos M et al (2006) Nuclear receptors Nur77, Nurr1, and NOR-1 expressed in atherosclerotic lesion macrophages reduce lipid loading and inflammatory responses. Arterioscler Thromb Vasc Biol 26(10):2288–2294

    Article  CAS  PubMed  Google Scholar 

  • Bora SH, Liu Z, Kecojevic A, Merchenthaler I, Koliatsos VE (2005) Direct, complex effects of estrogens on basal forebrain cholinergic neurons. Exp Neurol 194(2):506–522

    Article  CAS  PubMed  Google Scholar 

  • Bourque M, Dluzen DE, Di Paolo T (2012) Signaling pathways mediating the neuroprotective effects of sex steroids and SERMs in Parkinson’s disease. Front Neuroendocrinol 33(2):169–178

    Article  CAS  PubMed  Google Scholar 

  • Brott DA, Werkheiser JL, Campbell P, Bentley P, Andersson HH, Stewart J, Huby R, Altekar M, Kinter LB (2012) Inhibition of oestradiol-induced prolactin release in a dual-cannulated ovariectomized rat model by carmoxirole, a peripherally restricted dopamine agonist. Basic Clin Pharmacol Toxicol 111(6):411–416

    CAS  PubMed  Google Scholar 

  • Chan CR, Hsu JT, Chang IT, Young YC, Lin CM, Ying C (2007) The effects of glutamate can be attenuated by estradiol via estrogen receptor dependent pathway in rat adrenal pheochromocytoma cells. Endocrine 31(1):44–51

    Article  CAS  PubMed  Google Scholar 

  • Chang C, Kokontis J, Liao SS, Chang Y (1989) Isolation and characterization of human TR3 receptor: a member of steroid receptor superfamily. J Steroid Biochem 34(1–6):391–395

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Su Y, Run X, Sun Z, Wang T, Sun S, Liang Z (2013) Pretreatment of PC12 cells with 17β-estradiol prevents Aβ-induce down-regulation of CREB phosphorylation and prolongs inhibition of GSK-3β. J Mol Neurosci 50(3):394–401

    Article  CAS  PubMed  Google Scholar 

  • Chiasson K, Lahaie-Collins V, Bournival J, Delapierre B, Gélinas S, Martinoli MG (2006) Oxidative stress and 17-alpha- and 17-beta-estradiol modulate neurofilaments differently. J Molec Neurosci 30(3):297–310

    Article  CAS  PubMed  Google Scholar 

  • De Nicola AF, Brocca ME, Pietranera L, Garcia-Segura LM (2012) Neuroprotection and sex steroid hormones: evidence of estradiol-mediated protection in hypertensive encephalopathy. Mini Rev Med Chem 12(11):1081–1089

    Article  PubMed  Google Scholar 

  • De Silva S, Han S, Zhang X, Huston DP, Winoto A, Zheng B (2005) Reduction of the incidence and severity of collagen-induced arthritis by constitutive Nur77 expression in the T cell lineage. Arthritis Rheum 52(1):333–338

    Article  PubMed  Google Scholar 

  • Deutsch AJ, Angerer H, Fuchs TE, Neumeister P (2012) The nuclear orphan receptors NR4A as therapeutic target in cancer therapy. Anticancer Agents Med Chem 12(9):1001–1014

    Article  CAS  PubMed  Google Scholar 

  • Eells JB, Wilcots J, Sisk S, Guo-Ross SX (2012) NR4A gene expression is dynamically regulated in the ventral tegmental are dopamine neurons and is related to expression of dopamine neurotransmission genes. J Mol Neurosci 46(2):545–553

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Elzer JG, Muhammad S, Wintermantel TM, Regnier-Vigouroux A, Ludwig J, Schütz G, Schwaninger M (2010) Neuronal estrogen receptor-alpha mediates neuroprotection by 17 beta-estradiol. J Cereb Blood Flow Metab 30(5):935–942

    Article  CAS  PubMed  Google Scholar 

  • Etgen AM, Jover-Mengual T, Zukin RS (2011) Neuroprotective actions of estradiol and novel estrogen analogs in ischemia: translational implications. Front Neuroendocrinol 32(3):336–352

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ferrini M, Bisagno V, Piroli G, Grillo C, Deniselle MC, De Nicola AF (2002) Effects of estrogens on choline–acetyltransferase immunoreactivity and GAP-43 mRNA in the forebrain of young and aging male rats. Cell Mol Neurobiol 22(3):289–301

    Article  CAS  PubMed  Google Scholar 

  • Gagné B, Gélinas S, Bureau G, Lagacé B, Ramassamy C, Chiasson K, Valastro B, Martinoli MG (2003) Effects of estradiol, phytoestrogens, and Ginkgo biloba extracts against 1-methyl-4-phenyl-pyridine-induced oxidative stress. Endocrine 21(1):89–95

    Article  PubMed  Google Scholar 

  • Gallo D, De Stefano I, Grazia Prisco M, Scambia G, Ferrandina G (2012) Estrogen receptor beta in cancer: an attractive target for therapy. Curr Pharm Des 18(19):2734–2757

    Article  CAS  PubMed  Google Scholar 

  • Gélinas S, Martinoli MG (2002) Neuroprotective effect of estradiol and phytoestrogens on MPP+-induced cytotoxicity in neuronal PC12 cells. J Neurosci Res 70(1):90–96

    Article  PubMed  Google Scholar 

  • Gélinas S, Bureau G, Valastro B, Massicotte G, Cicchetti F, Chiasson K, Gagné B, Blanchet J, Martinoli MG (2004) Alpha and beta estradiol protect neuronal but not native PC12 cells from paraquat-induced oxidative stress. Neurotox Res 6(2):141–148

    Article  PubMed  Google Scholar 

  • Hamers AA, Vos M, Rassam F et al (2012) Bone marrow-specific deficiency of nuclear receptor Nur77 enhances atherosclerosis. Circ Res 110(3):428–438

    Article  CAS  PubMed  Google Scholar 

  • Hasan W, Smith HJ, Ting AY, Smith PG (2005) Estrogen alters trkA and p75 neurotrophin receptor expression within sympathetic neurons. J Neurobiol 65(2):192–204

    Article  CAS  PubMed  Google Scholar 

  • Haslam G, Wyatt D, Kitos PA (1988) Estimating the number of viable animal cells in multi-well cultures based on their lactate dehydrogenase activities. Cytotechnology 32:63–75

    Article  Google Scholar 

  • Hazel TG, Nathans D, Lau LF (1988) A gene inducible by serum growth factors encodes a member of the steroid and thyroid hormone receptor superfamily. Proc Natl Acad Sci USA 85(22):8444–8448

    Article  CAS  PubMed  Google Scholar 

  • Hellberg D (2012) Sex steroids and cervical cancer. Anticancer Res 32(8):3045–3054

    CAS  PubMed  Google Scholar 

  • Hsu HC, Zhou T, Mountz JD (2004) Nur77 family of nuclear hormone receptors. Curr Drug Targets Inflamm Allergy 3(4):413–423

    Article  CAS  PubMed  Google Scholar 

  • Huang HM, Yu JY, Ou HC, Jeng KC (2008) Effect of naloxone on the induction of immediately early genes following oxygen- and glucose-deprivation in PC12 cells. Neurosci Lett 438(2):252–256

    Article  CAS  PubMed  Google Scholar 

  • Jacobs CM, Boldingh KA, Slagsvold HH, Thoresen GH, Paulsen RE (2004) ERK2 prohibits apoptosis-induced subcellular translocation of orphan nuclear receptor NGFI-B/TR3. J Biol Chem 279(48):50097–50101

    Article  CAS  PubMed  Google Scholar 

  • Jayanthi S, Deng X, Ladenheim B, McCoy M, Cluster A, Cai N, Cadet J (2005) Calcineurin/NFAT-induced up-regulation of the Fas ligand/Fas death pathway is involved in methamphetamine-induced neuronal apoptosis. Proc Natl Acad Sci USA 102(3):868–873

    Article  CAS  PubMed  Google Scholar 

  • Jiang P, Zhang WY, Li HD, Cai HL, Xue Y (2013) Repeated haloperidol administration has no effect on vitamin D signaling but increases retinoid X receptors and Nur77 expression in rat prefront cortex. Cell Mol Neurobiol 33(3):309–312

    Article  CAS  PubMed  Google Scholar 

  • Katagiri Y, Takeda K, Yu ZX, Ferrans VJ, Ozato K, Guroff G (2000) Modulation of retinoid signalling through NGF-induced nuclear export of NGFI-B. Nat Cell Biol 2(7):435–440

    Article  CAS  PubMed  Google Scholar 

  • Kipp M, Amor S, Krauth R, Beyer C (2012) Multiple sclerosis: neuroprotective alliance of estrogen-progesterone and gender. Front Neuroendocrinol 33(1):1–16

    Article  CAS  PubMed  Google Scholar 

  • Lee SY, Park E, Kim SC, Ahn RS, Ko C, Lee K (2012) ERα/E2 signaling suppresses the expression of steroidogenic enzyme genes via cross-talk with orphan nuclear receptor Nur77 in the testes. Mol Cell Endocrinol 362(1–2):91–103

    Article  CAS  PubMed  Google Scholar 

  • Li H, Kolluri SK, Gu J et al (2000) Cytochrome c release and apoptosis induced by mitochondrial targeting of nuclear orphan receptor TR3. Science 289(5482):1159–1164

    Article  CAS  PubMed  Google Scholar 

  • Li QX, Ke N, Sundaram R, Wong-Staal F (2006) NR4A1, 2, 3—an orphan nuclear hormone receptor family involved in cell apoptosis and carcinogenesis. Histol Histopathol 21(5):533–540

    CAS  PubMed  Google Scholar 

  • Li XL, Cheng WD, Li J, Guo XL, Guo CJ, Meng XH, Sun SG, Wang LX (2008) Protective effect of estrogen on apoptosis in a cell culture model of Parkinson’s disease. Clin Invest Med 31(5):E258–E264

    CAS  PubMed  Google Scholar 

  • Li B, Sheng X, Song M et al (2012) Expression of nerve growth factor and its receptors TrkA and p75 in the uterus of wild female ground squirrel (Citellus dauricus Brandt). Gen Comp Endocrinol 176(1):62–69

    Article  CAS  PubMed  Google Scholar 

  • Liu ZG, Smith SW, McLaughlin KA, Schwartz LM, Osborne BA (1994) Apoptotic signals delivered through the T-cell receptor of a T-cell hybrid require the immediate-early gene nur77. Nature 367(6460):281–284

    Article  CAS  PubMed  Google Scholar 

  • Maheux J, Ethier I, Rouillard C, Lévesque D (2005) Induction patterns of transcription factors of the nur family (nurr1, nur77, and nor-1) by typical and atypical antipsychotics in the mouse brain: implication for their mechanism of action. J Pharmacol Exp Ther 313(1):460–473

    Article  CAS  PubMed  Google Scholar 

  • Maheux J, St-Hilaire M, Voyer D, Tirotta E, Borrelli E, Rouillard C, Rompré PP, Lévesque D (2012a) Dopamine D(2) antagonist-induced striatal Nur77 expression requires activation of mGlu5 receptors by cortical afferents. Front Pharmacol 3:153

    Article  PubMed Central  PubMed  Google Scholar 

  • Maheux J, Vuillier L, Mahfouz M, Rouillard C, Lévesque D (2012b) Modulation of haloperidol-induced patterns of the transcription factor Nur77 and Nor-1 expression by serotonergic and adrenergic drugs in the mouse brain. Int J Neuropsychopharmacol 15(4):509–521

    Article  CAS  PubMed  Google Scholar 

  • Mahmoudi S, Samadi P, Gilbert F, Ouattara B, Morissette M, Grégoire L, Rouillard C, Di Paolo T, Lévesque D (2009) Nur77 mRNA levels and L-Dopa-induced dyskinesias in MPTP monkeys treated with docosahexaenoic acid. Neurobiol Dis 36(1):213–222

    Article  CAS  PubMed  Google Scholar 

  • Mahmoudi S, Blanchet PJ, Lévesque D (2013) Haloperidol-induced striatal Nur77 expression in a non-human primate model of tardive dyskinesia. Eur J Neurosci. doi:10.1111/ejn.12198

  • Mangelsdorf DJ, Thummel C, Beato M et al (1995) The nuclear receptor superfamily: the second decade. Cell 83(6):835–839

    Article  CAS  PubMed  Google Scholar 

  • Mannella P, Sanchez AM, Giretti MS, Genazzani AR, Simoncini T (2009) Oestrogen and progestins differently prevent glutamate toxicity in cortical neurons depending on prior hormonal exposure via the induction of neural nitric oxide synthase. Steroids 74(8):650–656

    Article  CAS  PubMed  Google Scholar 

  • Marin R, Casañas V, Pérez JA, Fabelo N, Fernandez C, Diaz M (2013) Oestrogens as modulators of neuronal signalosomes and brain lipid homeostasis related to protection against neurodegeneration. J Neuroendocrinol. doi:10.1111/jne.12068

  • Maruoka H, Sasaya H, Shimamura Y, Nakatani Y, Shimoke K, Ikeuchi T (2010) Dibutyryl-cAMP up-regulates nur77 expression via histone modification during neurite outgrowth in PC12 cells. J Biochem 148(1):93–101

    Article  CAS  PubMed  Google Scholar 

  • Marzaioli V, McMorrow JP, Angerer H et al (2012) Histamine contributes to increased RANKL to osteoprotegerin ratio through altered nuclear receptor 4A activity in human chondrocytes. Arthritis Rheum 64(10):3290–3301

    Article  CAS  PubMed  Google Scholar 

  • Mathisen GH, Fallgren ÅB, Strøm BO, Boldingh Debernard KA, Mohebi BU, Paulsen RE (2011) Delayed translocation of NGFI-B/RXR in glutamate stimulated neurons allows late protection by 9-cis retinoic acid. Biochem Biophys Res Commun 414(1):90–95

    Article  CAS  PubMed  Google Scholar 

  • Milbrandt J (1988) Nerve growth factor induces a gene homologous to the glucocorticoid receptor gene. Neuron 1(3):183–188

    Article  CAS  PubMed  Google Scholar 

  • Mohan HM, Aherne CM, Rogers AC, Baird AW, Winter DC, Murphy EP (2012) Molecular pathways: the role of NR4A orphan nuclear receptors in cancer. Clin Cancer Res 18(12):3223–3228

    Article  CAS  PubMed  Google Scholar 

  • Mount MP, Zhang Y, Amini M, Callaghan S, Kulczycki J, Mao Z, Slack RS, Anisman H, Park DS (2013) Perturbation of transcription factor Nur77 expression mediated by myocyte enhancer factor 2D (MEF2D) regulates dopaminergic neuron loss in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). J Biol Chem 288(20):114362–114371

    Article  Google Scholar 

  • No H, Bang Y, Lim J, Kim SS, Choi HS, Choi HJ (2010) Involvement of induction and mitochondrial targeting of orphan nuclear receptor Nur77 in 6-OHDA-induced SH-SY5Y cell death. Neurochem Int 56(4):620–626

    Article  CAS  PubMed  Google Scholar 

  • Novak G, Gallo A, Zai CC et al (2010) Association of the orphan nuclear receptor NR4A1 with tardive dyskinesia. Psychiatr Genet 20(1):39–43

    Article  PubMed  Google Scholar 

  • Patel VA, Longacre A, Hsiao K, Fan H, Meng F, Mitchell JE, Rauch J, Ucker DS, Levine JS (2006) Apoptotic cells, at all stages of the death process, trigger characteristic signaling events that are divergent from and dominant over those triggered by necrotic cells: implications for the delayed clearance model of autoimmunity. J Biol Chem 281(8):4663–4670

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pereira JC Jr, Rocha e Silva IR, Pradella-Hallinan M (2012) Transient Willis-Ekbom’s disease (restless legs syndrome) during pregnancy may be caused by estradiol-mediated dopamine overmodulation. Med Hypotheses 80(2):205–208

    Article  PubMed  Google Scholar 

  • Petrovska S, Dejanova B, Jurisic V (2012) Estrogens: mechanisms of neuroprotective effects. J Physiol Biochem 68(3):455–460

    Article  CAS  PubMed  Google Scholar 

  • Prokai L, Rivera-Portalatin NM, Prokai-Tatrai K (2013) Quantitative structure-activity relationships predicting the antioxidant potency of 17β-estradiol-related polycyclic phenols to inhibit lipid peroxidation. Int J Mol Sci 14(1):1443–1454

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Renoir JM, Marsaud V, Lazennec G (2013) Estrogen receptor signaling as a target for novel breast cancer therapeutics. Biochem Pharmacol 85(4):449–465

    Article  CAS  PubMed  Google Scholar 

  • Rousseau J, Cossette L, Grenier S, Martinoli MG (2002) Modulation of prolactin expression by xenoestrogens. Gen Comp Endocrinol 126(2):175–182

    Article  CAS  PubMed  Google Scholar 

  • Sánchez MG, Morissette M, Di Paolo T (2013) Oestradiol modulation of serotonin reuptake transporter and serotonin metabolism in the brain of monkeys. J Neuroendocrinol 25(6):560–569

    Article  PubMed  Google Scholar 

  • Scharfman HE, Maclusky NJ (2013) Differential regulation of BDNF, synaptic plasticity and sprouting in the hippocampal mossy fiber pathway of male and female rats. Neuropharmacology. doi:10.1016/j.neuropharm.2013.04.029

  • Schmittgen TD, Zakrajsek BA (2000) Effect of experimental treatment on housekeeping gene expression: validation by real-time, quantitative RT-PCR. J Biochem Biophys Method 46(1–2):69–81

    Article  CAS  Google Scholar 

  • Siddiqui MA, Kashyap MP, Al-Khedhairy AA, Musarrat J, Khanna VK, Yadav S, Pant AB (2011) Protective potential of 17β-estradiol against co-exposure of 4-hydroxynonenal and 6-hydroxydopamine in PC12 cells. Hum Exp Toxicol 30(8):860–869

    Article  CAS  PubMed  Google Scholar 

  • Simpkins JW, Singh M, Brock C, Etgen AM (2012) Neuroprotection and estrogen receptors. Neuroendocrinology 96(2):119–130

    Article  CAS  PubMed  Google Scholar 

  • Singer CA, Pang PA, Dobie DJ, Dorsa DM (1996) Estrogen increases GAP-43 (neuromodulin) mRNA in the preoptic area of aged rats. Neurobiol Aging 17(4):661–663

    Article  CAS  PubMed  Google Scholar 

  • Singh M, Meyer EM, Simpkins JW (1995) The effect of ovariectomy and estradiol replacement on brain-derived neurotrophic factor messenger ribonucleic acid expression in cortical and hippocampal brain regions of female sprague-dawley rats. Endocrinology 136(5):2320–2324

    Article  CAS  PubMed  Google Scholar 

  • St-Hilaire M, Landry E, Lévesque D, Rouillard C (2005) Denervation and repeated L-DOPA induce complex regulatory changes in neurochemical phenotypes of striatal neurons: implication of a dopamine D1-dependent mechanism. Neurobiol Dis 2(2):450–460

    Article  Google Scholar 

  • Suzuki S, Suzuki N, Mirtsos C et al (2003) Nur77 as a survival factor in tumor necrosis factor signaling. Proc Natl Acad Sci USA 100(14):8276–8280

    Article  CAS  PubMed  Google Scholar 

  • Suzuki S, Brown CM, Wise PM (2006) Mechanisms of neuroprotection by estrogen. Endocrine 29(2):209–215

    Article  CAS  PubMed  Google Scholar 

  • Tian X, Kai L, Hockberger PE, Wokosin DL, Surmeier DJ (2010) MEF-2 regulates activity-dependent spine loss in striatopallidal medium spiny neurons. Mol Cell Neurosci 44(1):94–108

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • To SK, Zeng JZ, Wong AS (2012) Nur77: a potential therapeutic target in cancer. Expert Opin Ther Targets 16(6):573–585

    Article  CAS  PubMed  Google Scholar 

  • Vest RS, Pike CJ (2012) Gender, sex steroid hormones, and Alzheimer’s disease. Horm Behav 63(2):301–307

    Article  PubMed  Google Scholar 

  • Wade J, Peabody C, Tang YP, Qi L, Burnett R (2013) Estradiol modulates neurotransmitter concentrations in the developing zebra finch song system. Brain Res 1517:87–92

    Article  CAS  PubMed  Google Scholar 

  • Winterle JS, Mill T, Harris T, Goldbeck RA (2001) Absolute kinetic characterization of 17-beta-estradiol as a radical-scavenging, antioxidant synergist. Arch Biochem Biophys 392(2):233–244

    Article  CAS  PubMed  Google Scholar 

  • Woronicz JD, Lina A, Calnan BJ, Szychowski S, Cheng L, Winoto A (1995) Regulation of the Nur77 orphan steroid receptor in activation-induced apoptosis. Mol Cell Biol 15(11):6364–6376

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wu H, Lin Y, Li W et al (2010) Regulation of Nur77 expression by beta-catenin and its mitogenic effect in colon cancer cells. FASEB J 25(1):192–205

    Article  PubMed  Google Scholar 

  • Zhang XK (2007) Targeting Nur77 translocation. Expert Opin Ther Targets 11(1):69–79

    Article  CAS  PubMed  Google Scholar 

  • Zorrilla Zubilete MA, Guelman LR, Maur DG, Caceres LG, Rios H, Zieher LM, Genaro AM (2010) Partial neuroprotection by 17-β-estradiol in neonatal γ-irradiated rat cerebellum. Neurochem Int 58(3):273–280

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was founded by a NSERC (Canada) grant to MGM and a CIHR (Canada) grant to CR. JR is a NSERC-Vanier student fellow and JB holds a FRSQ (Québec) studentship.

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Correspondence to Maria-Grazia Martinoli.

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Renaud, J., Chiasson, K., Bournival, J. et al. 17β-Estradiol Delays 6-OHDA-Induced Apoptosis by Acting on Nur77 Translocation from the Nucleus to the Cytoplasm. Neurotox Res 25, 124–134 (2014). https://doi.org/10.1007/s12640-013-9442-z

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