Skip to main content

Advertisement

SpringerLink
Log in

Nurr1 and PPARγ protect PC12 cells against MPP+ toxicity: involvement of selective genes, anti-inflammatory, ROS generation, and antimitochondrial impairment

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Parkinson’s disease (PD) can degenerate dopaminergic (DA) neurons in midbrain, substantia-nigra pars compacta. Alleviation of its symptoms and protection of normal neurons against degeneration are the main aspects of researches to establish novel therapeutic strategies. PPARγ as a member of PPARs have shown neuroprotection in a number of neurodegenerative disorders such as Alzheimer’s disease and PD. Nuclear receptor related 1 protein (Nurr1) is, respectively, member of NR4A family and has received great attentions as potential target for development, maintenance, and survival of DA neurons. Based on neuroprotective effects of PPARγ and dual role of Nurr1 in anti-inflammatory pathways and development of DA neurons, we hypothesize that PPARγ and Nurr1 agonists alone and in combined form can be targets for neuroprotective therapeutic development for PD in vitro model. 1-Methyl-4-phenylpyridinium (MPP+) induced neurotoxicity in PC12 cells as an in vitro model for PD studies. Treatment/cotreatment with PPARγ and Nurr1 agonists 24 h prior to MPP+ induction enhanced the viability of PC12 cell. The viability of PC12 cells was determined by MTS test. Mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (ROS) were detected by flow cytometry. In addition, the relative expression of four genes including TH (the marker of DA neurons), Ephrin A1, Nurr1, and Ferritin light chain were assessed by RT-qPCR. In the MPP+-pretreated PC12 cells, PPARγ and Nurr1 agonists and their combined form resulted in a decrease in the cell death rate. Moreover, production of intracellular ROS and MMP modulated by MPP+ was decreased by PPARγ and Nurr1 agonists’ treatment alone and in the combined form.

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

Similar content being viewed by others

Abbreviations

6-MP:

6-Mercaptopurine

AD:

Alzheimer’s disease

CREB:

cAMP response element binding

DA:

Dopaminergic

DAPI:

4′, 6-Diamidino-2-phenylindole

DCF:

2′, 7′-Dichlorofluorescin

DCFH2-DA:

6-Carboxy-2′, 7′-dichlorodihydrofluorescein diacetate

DMSO:

Dimethyl sulfoxide

DMEM:

Dulbecco’s modified eagle medium

ETS:

Electron transfer system

FITC:

Fluoroisothiocyanate

FTL:

Ferritin light chain

JC-1:

J-aggregate-forming fluorescent dye, 5, 5′, 6, 6′-tetrachloro-1, 1′, 3, 3′-tetraethylbenzimidazolocarbocyanine

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

IL-1β:

Interleukin 1 beta

LBD:

Lewy body dementia

MMP:

Mitochondrial membrane potential

MPP+ :

1-Methyl-4-phenylpyridinium ion

MPTP:

1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine

NGF:

Nerve growth factor

PD:

Parkinson’s disease

PGC1-α:

PPARγ coactivator 1α

PMS:

Phenazine methosulfate

PPARγ:

Peroxisome proliferator-activated receptor gamma

ROS:

Reactive oxygen species

SNpc:

Substantia-nigra pars compacta

SVZ:

Subventricular zone

TBBPA:

Tetrabromobisphenol A (2,2-bis(4-hydroxy-3,5-dibromophenyl)propane

TH:

Tyrosine hydroxylase

TNF-α:

Tumor necrosis alpha

TRITC:

Tetramethyl rhodamine-isothiocyanate

References

  1. De Lau LM, Breteler MM (2006) Epidemiology of Parkinson’s disease. Lancet neurol 5:525–535

    Article  PubMed  Google Scholar 

  2. Jenner P (2003) Oxidative stress in Parkinson’s disease. Ann Neurol 53:S26–S36

    Article  CAS  PubMed  Google Scholar 

  3. Jodeiri Farshbaf M, Ghaedi K, Megraw TL, Curtiss J, Shirani Faradonbeh M, Vaziri P et al (2016) Does PGC1α/FNDC5/BDNF elicit the beneficial effects of exercise on neurodegenerative disorders? Neuromol Med 18(1):1–15

    Article  CAS  Google Scholar 

  4. Schulz JB, Falkenburger BH (2004) Neuronal pathology in Parkinson’s disease. Cell Tissue Res 318(1):135–147

    Article  PubMed  Google Scholar 

  5. Desvergne B, Wahli W (1999) Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev 20(5):649–688

    CAS  PubMed  Google Scholar 

  6. Delerive P, Fruchart JC, Staels B (2001) Peroxisome proliferator-activated receptors in inflammation control. J Endocrinol 169(3):453–459

    Article  CAS  PubMed  Google Scholar 

  7. Combs CK, Johnson DE, Karlo JC, Cannady SB, Landreth GE (2000) Inflammatory mechanisms in Alzheimer’s disease: inhibition of beta-amyloid-stimulated proinflammatory responses and neurotoxicity by PPARgamma agonists. J Neurosci 20:558–567

    CAS  PubMed  Google Scholar 

  8. Nicolakakis N, Aboulkassim T, Ongali B, Lecrux C, Fernandes P, Rosa-Neto P et al (2008) Complete rescue of cerebrovascular function in aged Alzheimer’s disease transgenic mice by antioxidants and pioglitazone, a peroxisome proliferator-activated receptor gamma agonist. J Neurosci 28(37):9287–9296

    Article  CAS  Google Scholar 

  9. Wojtowicz AK, Szychowski KA, Kajta M (2014) PPAR-γ agonist GW1929 but not antagonist GW9662 reduces TBBPA-induced neurotoxicity in primary neocortical cells. Neurotox Res 5:311–322

    Article  Google Scholar 

  10. Kaundal RK, Sharma SS (2011) Ameliorative effects of GW1929, a nonthiazolidinedione PPARγ agonist, on inflammation and apoptosis in focal cerebral ischemic-reperfusion injury. Curr Neurovasc Res 8:236–245

    Article  CAS  PubMed  Google Scholar 

  11. Dehmer T, Heneka MT, Sastre M, Dichgans J, Schulz JB (2004) Protection by pioglitazone in the MPTP model of Parkinson’s disease correlates with I kappa B alpha induction and block of NF kappa B and iNOS activation. J Neurochem 88:494–501

    Article  CAS  PubMed  Google Scholar 

  12. Feinstein DL, Spagnolo A, Akar C, Weinberg G, Murphy P, Gavrilyuk V et al (2005) Receptor-independent actions of PPAR thiazolidinedione agonists: is mitochondrial function the key? Biochem Pharmacol 70:177–188

    Article  CAS  PubMed  Google Scholar 

  13. Kim CH, Han BS, Moon J, Kim DJ, Shin J, Rajan S et al (2015) Nuclear receptor Nurr1 agonists enhance its dual functions and improve behavioral deficits in an animal model of Parkinson’s disease. Proc Natl Acad Sci USA 112:8756–8761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Jankovic J, Chen S, Le WD (2005) The role of Nurr1 in the development of dopaminergic neurons in Parkinson’s disease. Prog Neurobiol 77:128–138

    Article  CAS  PubMed  Google Scholar 

  15. Ordentlich P, Yan Y, Zhou S, Heyman R (2003) An identification of the antineoplastic agent 6-mercaptopurine as an activator of the orphan nuclear hormone receptor Nurr1. J Biol Chem 278:24791–24799

    Article  CAS  PubMed  Google Scholar 

  16. Saijo K, Winner B, Carson CT, Collier JG, Boyer L, Rosenfeld MG et al (2009) A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell 137(1):47–59

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH (2010) Mechanisms underlying inflammation in neurodegeneration. Cell 140(6):918–934

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Shi Y (2007) Orphan nuclear receptors in drug discovery. Drug Discov Today 12(11–12):440–445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Yan J, Sun J, Huang L, Fu Q, Du G (2014) Simvastatin prevents neuroinflammation by inhibiting N-methyl-d-aspartic acid receptor 1 in 6-hydroxydopamine-treated PC12 cells. J Neurosci Res 92:634–640

    Article  CAS  PubMed  Google Scholar 

  20. Jing X, Miwa H, Sawada T, Nakanishi I, Kondo T, Miyajima M et al (2012) Ephrin-A1-mediated dopaminergic neurogenesis and angiogenesis in a rat model of Parkinson’s disease. PLoS One 7:e32019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Men T, Piao SH, Teng CB (2013) Regulation of differentiation of mesenchymal stem cells by the Hippo pathway effectors TAZ/YAP. Yi Chuan 35:1283–1290

    Article  CAS  PubMed  Google Scholar 

  22. Parkinson GM, Dayas CV, Smith DW (2015) Age-related gene expression changes in substantia nigra dopamine neurons of the rat. Mech Ageing Dev 149:41–49

    Article  CAS  PubMed  Google Scholar 

  23. Praticó D, Pasin M, Barry OP, Ghiselli A, Sabatino G, Iuliano L et al (1999) Iron-dependent human platelet activation and hydroxyl radical formation: involvement of protein kinase C. Circulation 99(24):3118–3124

    Article  PubMed  Google Scholar 

  24. Dusek P, Schneider SA, Aaseth J (2016) Iron chelation in the treatment of neurodegenerative diseases. J Trace Elem Med Biol. doi:10.1016/j.jtemb.2016.03.010

    PubMed  Google Scholar 

  25. Arosio P, Levi S (2010) Cytosolic and mitochondrial ferritins in the regulation of cellular iron homeostasis and oxidative damage. Biochim Biophys Acta 1800(8):783–792

    Article  CAS  PubMed  Google Scholar 

  26. Harrison PM, Arosio P (1996) The ferritins: molecular properties, iron storage function and cellular regulation. Biochim Biophys Acta 1275:161–203

    Article  PubMed  Google Scholar 

  27. Vidal R, Ghetti B, Takao M, Brefel-Courbon C, Uro-Coste E, Glazier BS et al (2004) Intracellular ferritin accumulation in neural and extraneural tissue characterizes a neurodegenerative disease associated with a mutation in the ferritin light polypeptide gene. J Neuropathol Exp Neurol 63(4):363–380

    Article  CAS  PubMed  Google Scholar 

  28. Shamah SM, Lin MZ, Goldberg JL, Estrach S, Sahin M, Hu L et al (2001) EphA receptors regulate growth cone dynamics through the novel guanine nucleotide exchange factor ephexin. Cell 105:233–244

    Article  CAS  PubMed  Google Scholar 

  29. Gerlai R (2001) Eph receptors and neural plasticity. Nat Rev Neurosci 2(3):205–209

    Article  CAS  PubMed  Google Scholar 

  30. Aoki M, Yamashita T, Tohyama M (2004) EphA receptors direct the differentiation of mammalian neural precursor cells through a mitogen-activated protein kinase-dependent pathway. J Biol Chem 279:32643–32650

    Article  CAS  PubMed  Google Scholar 

  31. Jing X, Miwa H, Sawada T, Nakanishi I, Kondo T, Miyajima M et al (2012) Ephrin-A1-mediated dopaminergic neurogenesis and angiogenesis in a rat model of Parkinson’s disease. PLoS One 7(2):e32019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Wang AG, Chen CH, Yang CW, Yen MY, Hsu WM, Liu JH et al (2002) Change of gene expression profiles in the retina following optic nerve injury. Brain Res Mol Brain Res 101(1–2):82–92

    Article  CAS  PubMed  Google Scholar 

  33. Zhang Z, Li X, Xie WJ, Tuo H, Hintermann S, Jankovic J et al (2012) Anti-parkinsonian effects of Nurr1 activator in ubiquitin–proteasome system impairment induced animal model of Parkinson’s disease. CNS Neurol Disord Drug Targets 11:768–773

    Article  CAS  PubMed  Google Scholar 

  34. Kim KS, Kim CH, Hwang DY, Seo H, Chung S, Hong SJ et al (2003) Orphan nuclear receptor Nurr1 directly transactivates the promoter activity of the tyrosine hydroxylase gene in a cell-specific manner. J Neurochem 85:622–634

    Article  CAS  PubMed  Google Scholar 

  35. Huot P, Lévesque M, Morissette M, Calon F, Dridi M, Di Paolo T et al (2008) L-Dopa treatment abolishes the numerical increase in striatal dopaminergic neurons in parkinsonian monkeys. J Chem Neuroanat 35(1):77–84

    Article  CAS  PubMed  Google Scholar 

  36. Dill J, Patel AR, Yang XL, Bachoo R, Powell CM, Li S (2010) A molecular mechanism for ibuprofen-mediated RhoA inhibition in neurons. J Neurosci 30:963–972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ghoochani A, Shabani K, Peymani M, Ghaedi K, Karamali F, Karbalaei K et al (2012) The influence of peroxisome proliferator-activated receptor γ1 during differentiation of mouse embryonic stem cells to neural cells. Differentiation 83:60–67

    Article  CAS  PubMed  Google Scholar 

  38. Peymani M, Ghoochani A, Ghaedi K, Karamali F, Karbalaie K, Kiani-Esfahani A et al (2013) Dual effects of peroxisome proliferator-activated receptor γ on embryonic stem cell self-renewal in presence and absence of leukemia inhibitory factor. Eur J Cell Biol 92:160–168

    Article  CAS  PubMed  Google Scholar 

  39. Vidal R, Miravalle L, Gao X, Barbeito AG, Baraibar MA, Hekmatyar SK et al (2008) Expression of a mutant form of the ferritin light chain gene induces neurodegeneration and iron overload in transgenic mice. J Neurosci 28:60–67

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Volakakis N, Kadkhodaei B, Joodmardi E, Wallis K, Panman L, Silvaggi J et al (2010) NR4A orphan nuclear receptors as mediators of CREB-dependent neuroprotection. Proc Natl Acad Sci USA 107:12317–12322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Fu AK, Ip NY (2007) Cyclin-dependent kinase 5 links extracellular cues to actin cytoskeleton during dendritic spine development. Cell Adhes Migr 1:110–112

    Article  Google Scholar 

  42. Quinn LP, Crook B, Hows ME, Vidgeon-Hart M, Chapman H, Upton N et al (2008) The PPARγ agonist pioglitazone is effective in the MPTP mouse model of Parkinson’s disease through inhibition of monoamine oxidase B. Br J Pharmacol 154:226–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Smith GA, Rocha EM, Rooney T, Barneoud P, McLean JR, Beagan J et al (2015) A Nurr1 agonist causes neuroprotection in a Parkinson’s disease lesion model primed with the toll-like receptor 3 dsRNA inflammatory stimulant poly(I:C). PLoS One 10:e0121072

    Article  PubMed  PubMed Central  Google Scholar 

  44. Remels AH, Langen RC, Gosker HR, Russell AP, Spaapen F, Voncken JW et al (2009) PPARγ inhibits NF-κB-dependent transcriptional activation in skeletal muscle. Am J Physiol Endocrinol Metabol 297:174–183

    Article  Google Scholar 

  45. Dubois C, Hengerer B, Mattes H (2006) Identification of a potent agonist of the orphan nuclear receptor Nurr1. Chem Med Chem 1:955–958

    Article  CAS  PubMed  Google Scholar 

  46. De Miranda BR, Popichak KA, Hammond SL, Miller JA, Safe S, Tjalkens RB (2015) Novel para-phenyl substituted diindolylmethanes protect against MPTP neurotoxicity and suppress glial activation in a mouse model of Parkinson’s disease. Toxicol Sci 143:360–373

    Article  PubMed  Google Scholar 

  47. Lou X, Liao W (2012) Association of Nurr1 gene mutations with Parkinson’s disease in the Han population living in the Hubei province of China. Neural Regen Res 7(23):1791–1796

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Esteves M, Cristóvão AC, Saraiva T, Rocha SM, Baltazar G, Ferreira L et al (2015) Retinoic acid-loaded polymeric nanoparticles induce neuroprotection in a mouse model for Parkinson’s disease. Front Aging Neurosci 7:20

    Article  PubMed  PubMed Central  Google Scholar 

  49. Curtis AR, Fey C, Morris CM, Bindoff LA, Ince PG, Chinnery PF et al (2001) Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease. Nat Genet 28(4):350–354

    Article  CAS  PubMed  Google Scholar 

  50. Friedman A, Arosio P, Finazzi D, Koziorowski D, Galazka-Friedman J (2011) Ferritin as an important player in neurodegeneration. Parkinsonism Relat Disord 17:423–430

    Article  PubMed  Google Scholar 

  51. Mounsey RB, Teismann P (2012) Chelators in the treatment of iron accumulation in Parkinson’s disease. Int J Cell Biol 2012:983245

    Article  PubMed  PubMed Central  Google Scholar 

  52. Li X, Jankovic J, Le W (2011) Iron chelation and neuroprotection in neurodegenerative diseases. J Neural Transm (Vienna) 118(3):473–477

    Article  CAS  Google Scholar 

  53. St-Pierre J, Drori S, Uldry M, Silvaggi JM, Rhee J, Jäger S et al (2006) Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 127:397–408

    Article  CAS  PubMed  Google Scholar 

  54. Lonze BE, Riccio A, Cohen S, Ginty DD (2002) Apoptosis, axonal growth defects, and degeneration of peripheral neurons in mice lacking CREB. Neuron 34:371–385

    Article  CAS  PubMed  Google Scholar 

  55. Wilkinson DG (2001) Multiple roles of Eph receptors and ephrins in neural development. Nat Rev Neurosci 2:155–164

    Article  CAS  PubMed  Google Scholar 

  56. Irani K, Goldschmidt-Clermont PJ (1998) Ras, superoxide and signal transduction. Biochem Pharmacol 55:1339–1346

    Article  CAS  PubMed  Google Scholar 

  57. Patt A, Harken AH, Burton LK, Rodell TC, Piermattei D, Schorr WJ et al (1988) Terada and LS Xanthine oxidase derived hydrogen peroxide contributes to ischemia reperfusion-induced edema in gerbil brains. J Clin Invest 81:1556–1562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Susin SA, Zamzami N, Kroemer G (1996) The cell biology of apoptosis: evidence for the implication of mitochondria. Apoptosis 1:231–242

    Article  Google Scholar 

  59. Troy CM, Salvesen GS (2002) Caspases on the brain. J Neurosci Res 69:145–150

    Article  CAS  PubMed  Google Scholar 

  60. Streit WJ, Mrak RE, Griffin WS (2004) Microglia and neuroinflammation: a pathological perspective. J Neuroinflamm 1(1):14

    Article  Google Scholar 

  61. Shastri A, Bonifati DM, Kishore U (2013) Innate immunity and neuroinflammation. Mediat Inflamm 2013:342931

    Article  Google Scholar 

  62. Frank-Cannon TC, Alto LT, McAlpine FE, Tansey MG (2009) Does neuroinflammation fan the flame in neurodegenerative diseases? Mol Neurodegener 4:47

    Article  PubMed  PubMed Central  Google Scholar 

  63. Mogi M, Togari A, Kondo T, Mizuno Y, Komure O, Kuno S et al (2000) Caspase activities and tumor necrosis factor receptor R1 (p55) level are elevated in the substantia nigra from parkinsonian brain. J Neural Transm (Vienna) 107(3):335–341

    Article  CAS  Google Scholar 

  64. Ghosh A, Roy A, Liu X, Kordower JH, Mufson EJ, Hartley DM et al (2007) Selective inhibition of NF-kappaB activation prevents dopaminergic neuronal loss in a mouse model of Parkinson’s disease. Proc Natl Acad Sci USA 104(47):18754–18759

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Mondal S, Roy A, Jana A, Ghosh S, Kordower JH, Pahan K (2012) Testing NF-κB-based therapy in hemiparkinsonian monkeys. J Neuroimmune Pharmacol 7(3):544–556

    Article  PubMed  PubMed Central  Google Scholar 

  66. Klesse LJ, Meyers KA, Marshall CJ, Parada LF (1999) Nerve growth factor induces survival and differentiation through two distinct signaling cascades in PC12 cells. Oncogene 18:2055–2068

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was funded by a grant-in-aid of research from Royan Institute awarded to Kamran Ghaedi, Ph.D. as the Principal Investigator (P.I.), and in support of Mohammad Jodeiri Farshbaf for obtaining his M.Sc. degree from the University of Isfahan.

Author information

Author notes

  1. Mohammad Jodeiri Farshbaf

    Present address: Department of Biology, New Mexico State University, Las Cruces, NM, USA

Authors and Affiliations

  1. Department of Biology, School of Sciences, University of Isfahan, Isfahan, 81746-73441, Iran

    Mohammad Jodeiri Farshbaf, Kamran Ghaedi, Maryam Noorbakhshnia & Soheila Rahgozar

  2. Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, 81593-58686, Iran

    Mahboobeh Forouzanfar, Kamran Ghaedi, Abbas Kiani-Esfahani, Maryam Peymani, Alireza Shoaraye Nejati, Tayebeh Izadi, Khadijeh Karbalaie & Mohammad Hossein Nasr-Esfahani

  3. Department of Molecular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran

    Mahboobeh Forouzanfar

  4. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, 19395-4644, Iran

    Hossein Baharvand

  5. Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran

    Hossein Baharvand

Authors
  1. Mohammad Jodeiri Farshbaf
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mahboobeh Forouzanfar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kamran Ghaedi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Abbas Kiani-Esfahani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maryam Peymani
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alireza Shoaraye Nejati
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tayebeh Izadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Khadijeh Karbalaie
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Maryam Noorbakhshnia
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Soheila Rahgozar
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hossein Baharvand
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Mohammad Hossein Nasr-Esfahani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Kamran Ghaedi, Hossein Baharvand or Mohammad Hossein Nasr-Esfahani.

Ethics declarations

Conflict of interest

None of the authors has any conflicts of interest to disclose and all authors support submission to this journal.

Ethical improvement statement

Approval for this study was obtained from the Institutional Review Board of Royan Institute (Tehran, Iran).

Additional information

Mohammad Jodeiri Farshbaf and Mahboobeh Forouzanfar contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

11010_2016_2764_MOESM1_ESM.tif

Supplementary Figure 1: Cell proliferation modulation by GW1929, 6-MP. PC12 cells were cultured in the presence different amounts of GW1929, 6-MP. Results were expressed as percentages of viable cells in relation to the control samples (Vehicle only). Represented values are the mean of duplicate independent experiments. (TIFF 155 kb)

11010_2016_2764_MOESM2_ESM.tif

Supplementary Figure 2: Apoptosis rate was decreased by pretreatment of the cells with GW1929, 6-MP. The number of annexin V positive cells was significantly decreased when GW1929, 6-MP and their combination were used. Results were expressed as the percentage of cell number after treating with MPP+. Represented values are the mean of triplicate independent experiments ±SEM. Similar alphabets indicate significant difference between same samples at p<0.05. (TIFF 151 kb)

11010_2016_2764_MOESM3_ESM.tif

Supplementary Figure 3: Quantification of PPARγ and Nurr1 intracellular distribution upon activation. Intracellular localization of PPARγ and Nurr1 in cells indicated predominantly nuclear-sorting [72% nuclear distribution vs. 28% cytosolic distribution for PPARγ and 85% nuclear distribution vs. 15% cytosolic distribution for Nurr1] after activation by GW1929 (10 μM) and 6-MP (0.5 µM), respectively, as compared with the untreated samples (-GW1929 and -6-MP) [14% nuclear distribution vs. 86% cytosolic distribution for PPARγ and 23% nuclear distribution vs. 77% cytosolic distribution for Nurr1]. (TIFF 151 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jodeiri Farshbaf, M., Forouzanfar, M., Ghaedi, K. et al. Nurr1 and PPARγ protect PC12 cells against MPP+ toxicity: involvement of selective genes, anti-inflammatory, ROS generation, and antimitochondrial impairment. Mol Cell Biochem 420, 29–42 (2016). https://doi.org/10.1007/s11010-016-2764-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-016-2764-4

Keywords

Search

Navigation