Prion protein lacks robust cytoprotective activity in cultured cells.

Molecular Neurodegeneration
Heather M Christensen, David A Harris

Abstract

The physiological function of the cellular prion protein (PrPC) remains unknown. However, PrPC has been reported to possess a cytoprotective activity that prevents death of neurons and other cells after a toxic stimulus. To explore this effect further, we attempted to reproduce several of the assays in which a protective activity of PrP had been previously demonstrated in mammalian cells. In the first set of experiments, we found that PrP over-expression had a minimal effect on the death of MCF-7 breast carcinoma cells treated with TNF-alpha and Prn-p0/0 immortalized hippocampal neurons (HpL3-4 cells) subjected to serum deprivation. In the second set of assays, we observed only a small difference in viability between cerebellar granule neurons cultured from PrP-null and control mice in response to activation of endogenous or exogenous Bax. Taken together, our results suggest either that cytoprotection is not a physiologically relevant activity of PrPC, or that PrPC-dependent protective pathways operative in vivo are not adequately modeled by these cell culture systems. We suggest that cell systems capable of mimicking the neurotoxic effects produced in transgenic mice by N-terminally deleted forms of PrP or Doppel may represent...Continue Reading

References

Jan 1, 1987·Breast Cancer Research and Treatment·C K OsborneJ M Trent
Jul 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·G ZanussoM S Sy
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·S B Prusiner
Dec 3, 1998·Revue neurologique·D Dormont
Apr 23, 1999·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·R K DomanN J Donato
Jul 27, 1999·Nature·C KuwaharaT Onodera
Feb 28, 2001·Proceedings of the National Academy of Sciences of the United States of America·H MoH J Dyson
Aug 28, 2001·The Journal of Biological Chemistry·Y BounharA LeBlanc
Dec 6, 2001·Proceedings of the National Academy of Sciences of the United States of America·R C MooreP Tremblay
Jan 10, 2002·Journal of Neuroscience Research·David R BrownLaura Canevari
Aug 14, 2003·Biochemical and Biophysical Research Communications·Akikazu SakudoTakashi Onodera
Aug 15, 2003·The Journal of Biological Chemistry·Xavier RoucouAndrea C LeBlanc
Oct 11, 2003·Biochemical and Biophysical Research Communications·Akikazu SakudoTakashi Onodera
Aug 11, 2004·Journal of Theoretical Biology·Emmanuel GarcionDidier Wion
Sep 24, 2004·International Journal of Cancer. Journal International Du Cancer·Jingping DuDaiming Fan
Dec 25, 2004·Proceedings of the National Academy of Sciences of the United States of America·Roberto ChiesaDavid A Harris
Jan 13, 2005·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Xavier Roucou, Andréa C LeBlanc
Jan 27, 2005·Biochemical and Biophysical Research Communications·Akikazu SakudoTakashi Onodera
Mar 9, 2005·The Journal of Biological Chemistry·Aimin Li, David A Harris
May 18, 2005·Biochemical and Biophysical Research Communications·Neville VassalloHans A Kretzschmar
Jun 14, 2005·Biochemical and Biophysical Research Communications·Akikazu SakudoTakashi Onodera
May 6, 2006·Neuron·David A Harris, Heather L True
May 19, 2006·Molecular Biology of the Cell·Angelika S RamboldJörg Tatzelt
Jul 21, 2006·Neurobiology of Disease·Muriel CoulpierMarc Eloit

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Methods Mentioned

BETA
transfection
flow cytometry
PCR
transgenic

Software Mentioned

MetaMorph
CELLQUEST
Primer Express

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