Skip to main content

Advertisement

SpringerLink
Log in

Parkin Modulates Gene Expression in Control and Ceramide-Treated PC12 Cells

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Mutations in the parkin gene cause autosomal-recessive early-onset parkinsonism as a result of the degeneration of mesencephalic dopaminergic neurons. In cell culture models, parkin expression has been shown to protect against cell death mediated by the sphingolipid ceramide. To determine whether the antiapoptotic effect of parkin involves changes in gene expression, we used Affymetrix oligonucleotide microarrays to analyse gene expression in stably transfected PC12 cells which conditionally overexpress parkin, that were treated or not with C2-ceramide. Overexpression of parkin and ceramide treatment both modulated gene expression. A number of the genes upregulated in the presence of ceramide, and modulated by parkin, were associated with apoptosis or cellular stress reactions. We validated the upregulation of four such genes (CHK, EIF4EBP1, GADD45A and PTPN-5) by real-time PCR after 3, 6, 9 and 12 h of ceramide treatment in cells that overexpressed parkin or not. All were upregulated 2 to 11-fold, 3 and 6 h after application of ceramide. Parkin overexpression reduced the upregulation of EIF4EBP1, GADD45A and PTPN-5, but only at 6 h. These results suggest that, in this assay, the cytoprotective effect of parkin might result not only from its E3-ligase activity, but also from direct or indirect modulation of gene expression in a time-dependent manner.

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

Similar content being viewed by others

Abbreviations

CHK:

Choline kinase

EIF4EBP1:

Eukaryotic translation initiation factor 4e-binding protein 1

ESTs:

Expressed sequence tags

GADD45A:

Growth arrest- and DNA damage-inducible gene alpha

NGF:

Nerve growth factor

PD:

Parkinson’s disease

PPID:

Peptidyl-prolyl isomerase d

PTPN-5:

Protein-tyrosine phosphatase, nonreceptor-type, 5

References

  1. MH Polymeropoulos C Lavedan E Leroy SE Ide A Dehejia A Dutra B Pike H Root J Rubenstein R Boyer ES Stenroos S Chandrasekharappa A Athanassiadou T Papapetropoulos WG Johnson AM Lazzarini RC Duvoisin G Di Iorio LI Golbe RL Nussbaum (1997) Science 276 2045–2047 Occurrence Handle10.1126/science.276.5321.2045 Occurrence Handle9197268 Occurrence Handle1:CAS:528:DyaK2sXkt1altr4%3D

    Article  PubMed  CAS  Google Scholar 

  2. E Leroy R Boyer G Auburger B Leube G Ulm E Mezey G Harta MJ Brownstein S Jonnalagada T Chernova A Dehejia C Lavedan T Gasser PJ Steinbach KD Wilkinson MH Polymeropoulos (1998) Nature 395 451–452 Occurrence Handle10.1038/26652 Occurrence Handle9774100 Occurrence Handle1:CAS:528:DyaK1cXms1antLo%3D

    Article  PubMed  CAS  Google Scholar 

  3. A Zimprich B Muller-Myhsok M Farrer P Leitner M Sharma M Hulihan P Lockthart A Strongosky J Kachergus DB Calne J Stoessl RJ Uitti RF Pfeiffer C Trenkwalder N Homann E Ott K Wenzel F Asmus J Hardy Z Wszolek T Gasser (2004) Am. J. Hum. Genet. 74 11–19 Occurrence Handle10.1086/380647 Occurrence Handle14691730 Occurrence Handle1:CAS:528:DC%2BD2cXlvVOktg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  4. T Kitada S Asakawa N Hattori H Matsumine Y Yamamura S Minoshima M Yokochi Y Mizuno N Shimizu (1998) Nature 392 605–608 Occurrence Handle9560156 Occurrence Handle1:CAS:528:DyaK1cXis1Sqsrc%3D

    PubMed  CAS  Google Scholar 

  5. V Bonifati P Rizzu MJ Baren Particlevan O Schaap GJ Breedveld E Krieger MC Dekker F Squitieri P Ibanez M Joosse JW Dongen Particlevan N Vanacore JC Swieten Particlevan A Brice G Meco CM Duijn Particlevan BA Oostra P Heutink (2003) Science 299 256–259 Occurrence Handle10.1126/science.1077209 Occurrence Handle12446870 Occurrence Handle1:CAS:528:DC%2BD3sXhs1Gkuw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  6. EM Valente PM Abou-Sleiman V Caputo MM Muqit K Harvey S Gispert Z Ali D Del Turco AR Bentivoglio DG Healy A Albanese R Nussbaum R Gonzalez-Maldonado T Deller S Salvi P Cortelli WP Gilks DS Latchman RJ Harvey B Dallapiccola G Auburger NW Wood (2004) Science 304 1158–1160 Occurrence Handle10.1126/science.1096284 Occurrence Handle15087508 Occurrence Handle1:CAS:528:DC%2BD2cXktVyit7k%3D

    Article  PubMed  CAS  Google Scholar 

  7. CB Lucking A Durr V Bonifati J Vaughan G Michele ParticleDe T Gasser BS Harhangi G Meco P Denefle NW Wood Y Agid A Brice (2000) N. Engl. J. Med. 342 1560–1567 Occurrence Handle10.1056/NEJM200005253422103 Occurrence Handle10824074 Occurrence Handle1:CAS:528:DC%2BD3cXktVCgtbs%3D

    Article  PubMed  CAS  Google Scholar 

  8. Y Imai M Soda R Takahashi (2000) J. Biol. Chem. 275 35661–35664 Occurrence Handle10973942 Occurrence Handle1:CAS:528:DC%2BD3cXosVSksLo%3D

    PubMed  CAS  Google Scholar 

  9. H Shimura N Hattori S Kubo Y Mizuno S Asakawa S Minoshima N Shimizu K Iwai T Chiba K Tanaka T Suzuki (2000) Nat. Genet. 25 302–305 Occurrence Handle10888878 Occurrence Handle1:STN:280:DC%2BD3czptF2nsw%3D%3D

    PubMed  CAS  Google Scholar 

  10. Y Zhang J Gao KK Chung H Huang VL Dawson TM Dawson (2000) Proc. Natl. Acad. Sci. USA 97 13354–13359 Occurrence Handle11078524 Occurrence Handle1:CAS:528:DC%2BD3cXosVOjs7o%3D

    PubMed  CAS  Google Scholar 

  11. BI Giasson VM Lee (2003) Cell 114 1–8 Occurrence Handle10.1016/S0092-8674(03)00509-9 Occurrence Handle12859888 Occurrence Handle1:CAS:528:DC%2BD3sXlslWqsb4%3D

    Article  PubMed  CAS  Google Scholar 

  12. PJ Kahle U Leimer C Haass (2000) Trends Biochem. Sci. 25 524–527 Occurrence Handle10.1016/S0968-0004(00)01682-0 Occurrence Handle11084358 Occurrence Handle1:CAS:528:DC%2BD3cXotVKqtLg%3D

    Article  PubMed  CAS  Google Scholar 

  13. F Darios O Corti CB Lucking C Hampe MP Muriel N Abbas WJ Gu EC Hirsch T Rooney M Ruberg A Brice (2003) Hum. Mol. Genet. 12 517–526 Occurrence Handle10.1093/hmg/ddg044 Occurrence Handle12588799 Occurrence Handle1:CAS:528:DC%2BD3sXisFSlu7c%3D

    Article  PubMed  CAS  Google Scholar 

  14. DP Harkin JM Bean D Miklos YH Song VB Truong C Englert FC Christians LW Ellisen S Maheswaran JD Oliner DA Haber (1999) Cell 97 575–586 Occurrence Handle10.1016/S0092-8674(00)80769-2 Occurrence Handle10367887 Occurrence Handle1:CAS:528:DyaK1MXjs1yqtb0%3D

    Article  PubMed  CAS  Google Scholar 

  15. T Beissbarth K Fellenberg B Brors R Arribas-Prat J Boer NC Hauser M Scheideler JD Hoheisel G Schutz A Poustka M Vingron (2000) Bioinformatics 16 1014–1022 Occurrence Handle11159313 Occurrence Handle1:CAS:528:DC%2BD3MXptlOmuw%3D%3D

    PubMed  CAS  Google Scholar 

  16. H Jiang Y Ren J Zhao J Feng (2004) Hum. Mol. Genet. 13 1745–1754 Occurrence Handle15198987 Occurrence Handle1:CAS:528:DC%2BD2cXlvFGqsbw%3D

    PubMed  CAS  Google Scholar 

  17. JC Greene AJ Whitworth I Kuo LA Andrews MB Feany LJ Pallanck (2003) Proc. Natl. Acad. Sci. USA 100 4078–4083 Occurrence Handle10.1073/pnas.0737556100 Occurrence Handle12642658 Occurrence Handle1:CAS:528:DC%2BD3sXivFSqu70%3D

    Article  PubMed  CAS  Google Scholar 

  18. KK Chung B Thomas X Li O Pletnikova JC Troncoso L Marsh VL Dawson TM Dawson (2004) Science 304 1328–1331 Occurrence Handle10.1126/science.1093891 Occurrence Handle15105460 Occurrence Handle1:CAS:528:DC%2BD2cXkt1Ggu7c%3D

    Article  PubMed  CAS  Google Scholar 

  19. KK Chung Y Zhang KL Lim Y Tanaka H Huang J Gao CA Ross VL Dawson TM Dawson (2001) Nat. Med. 7 1144–1150 Occurrence Handle10.1038/nm1001-1144 Occurrence Handle11590439 Occurrence Handle1:CAS:528:DC%2BD3MXns12kurg%3D

    Article  PubMed  CAS  Google Scholar 

  20. H Shimura MG Schlossmacher N Hattori MP Frosch A Trockenbacher R Schneider Y Mizuno KS Kosik DJ Selkoe (2001) Science 293 263–269 Occurrence Handle10.1126/science.1060627 Occurrence Handle11431533 Occurrence Handle1:CAS:528:DC%2BD3MXlt1yitL4%3D

    Article  PubMed  CAS  Google Scholar 

  21. MS Goldberg SM Fleming JJ Palacino C Cepeda HA Lam A Bhatnagar EG Meloni N Wu LC Ackerson GJ Klapstein M Gajendiran BL Roth MF Chesselet NT Maidment MS Levine J Shen (2003) J. Biol. Chem. 278 43628–43635 Occurrence Handle12930822 Occurrence Handle1:CAS:528:DC%2BD3sXosFSrsbk%3D

    PubMed  CAS  Google Scholar 

  22. CE Chalfant K Rathman RL Pinkerman RE Wood LM Obeid B Ogretmen YA Hannun (2002) J. Biol. Chem. 277 12587–12595 Occurrence Handle10.1074/jbc.M112010200 Occurrence Handle11801602 Occurrence Handle1:CAS:528:DC%2BD38XivV2qurY%3D

    Article  PubMed  CAS  Google Scholar 

  23. BJ Kroesen B Pettus C Luberto M Busman H Sietsma L Leij Particlede YA Hannun (2001) J. Biol. Chem. 276 13606–13614 Occurrence Handle11278517 Occurrence Handle1:CAS:528:DC%2BD3MXjt12kt7c%3D

    PubMed  CAS  Google Scholar 

  24. PP Michel N Lambeng M Ruberg (1999) Clin. Neuropharmacol. 22 137–150 Occurrence Handle10367178 Occurrence Handle1:CAS:528:DyaK1MXjvFOnsbg%3D

    PubMed  CAS  Google Scholar 

  25. PJ Hartfield GC Mayne AW Murray (1997) FEBS Lett. 401 148–152 Occurrence Handle10.1016/S0014-5793(96)01460-3 Occurrence Handle9013876 Occurrence Handle1:CAS:528:DyaK2sXmsVCktA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  26. DA Wiesner G Dawson (1996) Glycoconj. J. 13 327–333 Occurrence Handle10.1007/BF00731508 Occurrence Handle8737258 Occurrence Handle1:CAS:528:DyaK28XisVOmsrw%3D

    Article  PubMed  CAS  Google Scholar 

  27. V France-Lanord B Brugg PP Michel Y Agid M Ruberg (1997) J. Neurochem. 69 1612–1621 Occurrence Handle9326290 Occurrence Handle1:CAS:528:DyaK2sXmsVCksbs%3D

    PubMed  CAS  Google Scholar 

  28. N Lambeng PP Michel B Brugg Y Agid M Ruberg (1999) Brain Res. 821 60–68 Occurrence Handle10.1016/S0006-8993(99)01061-6 Occurrence Handle10064788 Occurrence Handle1:CAS:528:DyaK1MXht1Ohsr0%3D

    Article  PubMed  CAS  Google Scholar 

  29. S Hunot B Brugg D Ricard PP Michel MP Muriel M Ruberg BA Faucheux Y Agid EC Hirsch (1997) Proc. Natl. Acad. Sci. USA 94 7531–7536 Occurrence Handle10.1073/pnas.94.14.7531 Occurrence Handle9207126 Occurrence Handle1:CAS:528:DyaK2sXksFygsLo%3D

    Article  PubMed  CAS  Google Scholar 

  30. C Decraene B Brugg M Ruberg E Eveno C Matingou F Tahi J Mariani C Auffray G Pietu (2002) Genome Biol. 3 RESEARCH0042 Occurrence Handle10.1186/gb-2002-3-8-research0042 Occurrence Handle12186649

    Article  PubMed  Google Scholar 

  31. MB Soares MF Bonaldo P Jelene L Su L Lawton A Efstratiadis (1994) Proc. Natl. Acad. Sci. USA 91 9228–9232 Occurrence Handle7937745 Occurrence Handle1:CAS:528:DyaK2cXmvFeqsrY%3D

    PubMed  CAS  Google Scholar 

  32. Z Cui M Houweling (2002) Biochim. Biophys. Acta 1585 87–96 Occurrence Handle12531541 Occurrence Handle1:CAS:528:DC%2BD3sXivVOqsw%3D%3D

    PubMed  CAS  Google Scholar 

  33. R Hernandez-Alcoceba L Saniger J Campos MC Nunez F Khaless MA Gallo A Espinosa JC Lacal (1997) Oncogene 15 2289–2301 Occurrence Handle9393874 Occurrence Handle1:CAS:528:DyaK2sXnsFajsbw%3D

    PubMed  CAS  Google Scholar 

  34. A Rodriguez-Gonzalez A Ramirez de Molina F Fernandez JC Lacal (2004) Oncogene 23 8247–8259 Occurrence Handle15378008 Occurrence Handle1:CAS:528:DC%2BD2cXovFOgsrY%3D

    PubMed  CAS  Google Scholar 

  35. S Pyronnet N Sonenberg (2001) Curr. Opin. Genet. Dev. 11 13–18 Occurrence Handle10.1016/S0959-437X(00)00150-7 Occurrence Handle11163145 Occurrence Handle1:CAS:528:DC%2BD3MXhtFSnt7w%3D

    Article  PubMed  CAS  Google Scholar 

  36. B Raught AC Gingras (1999) Int. J. Biochem. Cell Biol. 31 43–57 Occurrence Handle10.1016/S1357-2725(98)00131-9 Occurrence Handle10216943 Occurrence Handle1:CAS:528:DyaK1MXhvFSlu7g%3D

    Article  PubMed  CAS  Google Scholar 

  37. TL Deckwerth EM Johnson SuffixJr (1993) J. Cell Biol. 123 1207–1222 Occurrence Handle10.1083/jcb.123.5.1207 Occurrence Handle7503996 Occurrence Handle1:CAS:528:DyaK3sXmsVWqu7g%3D

    Article  PubMed  CAS  Google Scholar 

  38. I Mothe-Satney GJ Brunn LP McMahon CT Capaldo RT Abraham JC Lawrence SuffixJr (2000) J. Biol. Chem. 275 33836–33843 Occurrence Handle10.1074/jbc.M006005200 Occurrence Handle10942774 Occurrence Handle1:CAS:528:DC%2BD3cXnvVyjt7w%3D

    Article  PubMed  CAS  Google Scholar 

  39. BB Zhou H Li J Yuan MW Kirschner (1998) Proc. Natl. Acad. Sci. USA 95 6785–6790 Occurrence Handle9618490 Occurrence Handle1:CAS:528:DyaK1cXjslynur4%3D

    PubMed  CAS  Google Scholar 

  40. S Li N Sonenberg AC Gingras M Peterson S Avdulov VA Polunovsky PB Bitterman (2002) Mol. Cell Biol. 22 2853–2861 Occurrence Handle11909977 Occurrence Handle1:CAS:528:DC%2BD38XislWnt7s%3D

    PubMed  CAS  Google Scholar 

  41. VA Polunovsky IB Rosenwald AT Tan J White L Chiang N Sonenberg PB Bitterman (1996) Mol. Cell Biol. 16 6573–6581 Occurrence Handle8887686 Occurrence Handle1:CAS:528:DyaK28XmsVSjsb8%3D

    PubMed  CAS  Google Scholar 

  42. A Tan P Bitterman N Sonenberg M Peterson V Polunovsky (2000) Oncogene 19 1437–1447 Occurrence Handle10.1038/sj.onc.1203446 Occurrence Handle10723135 Occurrence Handle1:CAS:528:DC%2BD3cXit1ygtb8%3D

    Article  PubMed  CAS  Google Scholar 

  43. MM Karim JM Hughes J Warwicker GC Scheper CG Proud JE McCarthy (2001) J. Biol. Chem. 276 20750–20757 Occurrence Handle11278829 Occurrence Handle1:CAS:528:DC%2BD3MXktlKmsr0%3D

    PubMed  CAS  Google Scholar 

  44. VA Polunovsky AC Gingras N Sonenberg M Peterson A Tan JB Rubins JC Manivel PB Bitterman (2000) J. Biol. Chem. 275 24776–24780 Occurrence Handle10.1074/jbc.M001938200 Occurrence Handle10811643 Occurrence Handle1:CAS:528:DC%2BD3cXlsl2jtrk%3D

    Article  PubMed  CAS  Google Scholar 

  45. MS Sheikh MC Hollander AJ Fornance SuffixJr (2000) Biochem. Pharmacol. 59 43–45 Occurrence Handle10.1016/S0006-2952(99)00291-9 Occurrence Handle10605933 Occurrence Handle1:CAS:528:DC%2BD3cXhtV2htg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  46. M Takekawa H Saito (1998) Cell 95 521–530 Occurrence Handle10.1016/S0092-8674(00)81619-0 Occurrence Handle9827804 Occurrence Handle1:CAS:528:DyaK1cXns1ektrc%3D

    Article  PubMed  CAS  Google Scholar 

  47. PJ Lombroso G Murdoch M Lerner (1991) Proc. Natl. Acad. Sci. USA 88 7242–7246 Occurrence Handle1714595 Occurrence Handle1:CAS:528:DyaK38Xks1Gntrc%3D

    PubMed  CAS  Google Scholar 

  48. LM Boulanger PJ Lombroso A Raghunathan MJ During P Wahle JR Naegele (1995) J. Neurosci. 15 1532–1544 Occurrence Handle7869116 Occurrence Handle1:CAS:528:DyaK2MXjvVCgtbk%3D

    PubMed  CAS  Google Scholar 

  49. S Paul AC Nairn P Wang PJ Lombroso (2003) Nat. Neurosci. 6 34–42 Occurrence Handle10.1038/nn989 Occurrence Handle12483215 Occurrence Handle1:CAS:528:DC%2BD38Xps1Siurw%3D

    Article  PubMed  CAS  Google Scholar 

  50. JJ Palacino D Sagi MS Goldberg S Krauss C Motz M Wacker J lose J Shen (2004) J. Biol. Chem. 279 18614–18622 Occurrence Handle10.1074/jbc.M401135200 Occurrence Handle14985362 Occurrence Handle1:CAS:528:DC%2BD2cXjsVKmsrc%3D

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Klinik für Neurologie, Ludwig-Maximilians-Universität, Marchioninistr. 15, 81377, München, Germany

    P. G. Unschuld, J. Dächsel, E. Casademunt, K. Lehmann-Horn, M. Dichgans & C. B. Lücking

  2. Medizinische Klinik III, Ludwig-Maximilians-Universität, München, Germany

    A. Kohlmann

  3. Hôpital de la Salpêtrière, INSERM U679, Paris, France

    F. Darios, M. Ruberg & A. Brice

  4. Hertie-Institut für klinische Hirnforschung am Zentrum für Neurologie der Universität Tübingen, Germany

    T. Gasser

Authors
  1. P. G. Unschuld
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Dächsel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. Darios
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Kohlmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E. Casademunt
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K. Lehmann-Horn
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Dichgans
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. Ruberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A. Brice
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. T. Gasser
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. C. B. Lücking
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. B. Lücking.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Unschuld, P.G., Dächsel, J., Darios, F. et al. Parkin Modulates Gene Expression in Control and Ceramide-Treated PC12 Cells. Mol Biol Rep 33, 13–32 (2006). https://doi.org/10.1007/s11033-005-3961-5

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-005-3961-5

Keywords

Search

Navigation