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Pin1 levels are downregulated during ER stress in human neuroblastoma cells

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Abstract

Previously, we showed that pretangle neurons in Alzheimer’s disease (AD) brain display unfolded protein stress in the endoplasmic reticulum (ER). Others showed that the peptidylprolyl isomerase Pin1 protects against tangle formation by facilitating tau dephosphorylation, corroborating with the lower expression of Pin1 observed in tangle-bearing neurons. In this study, we investigated Pin1 expression under ER stress conditions. We show that in human, but not mouse neuroblastoma cells, Pin1 is downregulated in response to ER stress, in accordance with the presence of an ER stress response element in the mouse, but not the human Pin1 gene. This study creates a starting point to investigate whether modulation of the ER stress response may prevent or delay tau pathology in AD.

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References

  1. Selkoe DJ (2004) Cell biology of protein misfolding: the examples of Alzheimer’s and Parkinson’s diseases. Nat Cell Biol 6:1054–1061

    Article  PubMed  CAS  Google Scholar 

  2. McCracken AA, Brodsky JL (2003) Evolving questions and paradigm shifts in endoplasmic-reticulum-associated degradation (ERAD). Bioessays 25:868–877

    Article  PubMed  CAS  Google Scholar 

  3. Rutkowski DT, Kaufman RJ (2004) A trip to the ER: coping with stress. Trends Cell Biol 14:20–28

    Article  PubMed  CAS  Google Scholar 

  4. Yoshida H, Haze K, Yanagi H et al (1998) Identification of the cis-acting endoplasmic reticulum stress response element responsible for transcriptional induction of mammalian glucose-regulated proteins. Involvement of basic leucine zipper transcription factors. J Biol Chem 273:33741–33749

    Article  PubMed  CAS  Google Scholar 

  5. Wang Y, Shen J, Arenzana N et al (2000) Activation of ATF6 and an ATF6 DNA binding site by the endoplasmic reticulum stress response. J Biol Chem 275:27013–27020

    PubMed  CAS  Google Scholar 

  6. Roy B, Lee AS (1999) The mammalian endoplasmic reticulum stress response element consists of an evolutionarily conserved tripartite structure and interacts with a novel stress-inducible complex. Nucleic Acids Res 27:1437–1443

    Article  PubMed  CAS  Google Scholar 

  7. Scheper W, Hol EM (2005) Protein quality control in Alzheimer’s disease: a fatal saviour. Curr Drug Targets CNS Neurol Disord 4:283–292

    Article  PubMed  CAS  Google Scholar 

  8. Hoozemans JJ, Veerhuis R, Rozemuller AJ et al (2005) The unfolded protein response is activated in Alzheimer’s disease. Acta Neuropathol (Berl) 110:165–172

    Article  CAS  Google Scholar 

  9. Mandelkow EM, Mandelkow E (1998) Tau in Alzheimer’s disease. Trends Cell Biol 8:425–427

    Article  PubMed  CAS  Google Scholar 

  10. Lu PJ, Wulf G, Zhou XZ et al (1999) The prolyl isomerase Pin1 restores the function of Alzheimer-associated phosphorylated tau protein. Nature 399:784–788

    Article  PubMed  CAS  Google Scholar 

  11. Lu KP, Liou YC, Zhou XZ (2002) Pinning down proline-directed phosphorylation signaling. Trends Cell Biol 12:164–172

    Article  PubMed  CAS  Google Scholar 

  12. Liou YC, Sun A, Ryo A et al (2003) Role of the prolyl isomerase Pin1 in protecting against age-dependent neurodegeneration. Nature 424:556–561

    Article  PubMed  CAS  Google Scholar 

  13. Holzer M, Gartner U, Stobe A et al (2002) Inverse association of Pin1 and tau accumulation in Alzheimer’s disease hippocampus. Acta Neuropathol (Berl) 104:471–481

    CAS  Google Scholar 

  14. Hoozemans JJ, Stieler J, van Haastert ES et al (2006) The unfolded protein response affects neuronal cell cycle protein expression: implications for Alzheimer’s disease pathogenesis. Exp Gerontol 41:380–386

    Article  PubMed  CAS  Google Scholar 

  15. Ramakers C, Ruijter JM, Deprez RH et al (2003) Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data. Neurosci Lett 339:62–66

    Article  PubMed  CAS  Google Scholar 

  16. Pastorino L, Sun A, Lu PJ et al (2006) The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-beta production. Nature 440:528–534

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank our coworkers at the Neurogenetics Laboratory for their support and Dr. Elly Hol (Netherlands Institute for Brain Research) for the N2a cells. W. S. is supported by a career development grant of the Anton Meelmeijer Center for Translational Research. This work is supported by grant no. CGN05018 from the Hersenstichting Nederland to W. S..

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Authors and Affiliations

  1. Neurogenetics Laboratory, Academic Medical Center, P.O. Box 22700, Amsterdam, 1100 DE, The Netherlands

    Yolanda S. Kap, Adee J. Bodewes, Rob Zwart, Frank Baas & Wiep Scheper

  2. Department of Neuropathology, Academic Medical Center, Amsterdam, 1100 DE, The Netherlands

    Jeroen J. M. Hoozemans

  3. Department of Neurology, Academic Medical Center, Amsterdam, 1100 DE, The Netherlands

    Frank Baas

  4. Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University Medical Center, Leiden University, P.O. Box 9503, Leiden, 2300 RA, The Netherlands

    Onno C. Meijer

Authors
  1. Yolanda S. Kap
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  2. Jeroen J. M. Hoozemans
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  3. Adee J. Bodewes
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  4. Rob Zwart
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  5. Onno C. Meijer
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  6. Frank Baas
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  7. Wiep Scheper
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Correspondence to Wiep Scheper.

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Kap, Y.S., Hoozemans, J.J.M., Bodewes, A.J. et al. Pin1 levels are downregulated during ER stress in human neuroblastoma cells. Neurogenetics 8, 21–27 (2007). https://doi.org/10.1007/s10048-006-0060-2

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  • DOI: https://doi.org/10.1007/s10048-006-0060-2

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