Paradoxical role of prion protein aggregates in redox-iron induced toxicity.

PloS One
Dola DasNeena Singh

Abstract

Imbalance of iron homeostasis has been reported in sporadic Creutzfeldt-Jakob-disease (sCJD) affected human and scrapie infected animal brains, but the contribution of this phenotype to disease associated neurotoxicity is unclear. Using cell models of familial prion disorders, we demonstrate that exposure of cells expressing normal prion protein (PrP(C)) or mutant PrP forms to a source of redox-iron induces aggregation of PrP(C) and specific mutant PrP forms. Initially this response is cytoprotective, but becomes increasingly toxic with time due to accumulation of PrP-ferritin aggregates. Mutant PrP forms that do not aggregate are not cytoprotective, and cells show signs of acute toxicity. Intracellular PrP-ferritin aggregates induce the expression of LC3-II, indicating stimulation of autophagy in these cells. Similar observations are noted in sCJD and scrapie infected hamster brains, lending credence to these results. Furthermore, phagocytosis of PrP-ferritin aggregates by astrocytes is cytoprotective, while culture in astrocyte conditioned medium (CM) shows no measurable effect. Exposure to H(2)O(2), on the other hand, does not cause aggregation of PrP, and cells show acute toxicity that is alleviated by CM. These observation...Continue Reading

References

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
Dec 5, 1998·The Journal of Biological Chemistry·P C Pauly, D A Harris
Mar 10, 2000·Biochemical and Biophysical Research Communications·F H RuizN C Inestrosa
Apr 23, 2002·The Journal of Biological Chemistry·Ravi Shankar MishraNeena Singh
Jun 1, 2002·Current Opinion in Chemical Biology·Sylvain Lehmann
Oct 3, 2003·British Medical Bulletin·Pierluigi GambettiShu G Chen
Aug 11, 2004·Journal of Theoretical Biology·Emmanuel GarcionDidier Wion
Oct 22, 2004·Nature Reviews. Neuroscience·Luigi ZeccaRobert R Crichton
Jan 13, 2005·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Xavier Roucou, Andréa C LeBlanc
Mar 11, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Nam-Ho KimYong-Sun Kim
Aug 13, 2005·Acta Neuropathologica·Robert B PetersenGeorge Perry
Apr 25, 2006·Biological Research·Lorena Varela-NallarNibaldo C Inestrosa
May 6, 2006·Neuron·David A Harris, Heather L True
Sep 19, 2006·Nature Reviews. Microbiology·Adriano Aguzzi, Mathias Heikenwalder
Oct 20, 2006·Nature·Byron Caughey, Gerald S Baron
Feb 13, 2007·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Francisco Molina-HolgadoPaul Francis
Apr 25, 2007·Biochimica Et Biophysica Acta·Laura WestergardDavid A Harris
Jun 2, 2007·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Raj Kumar KoiriLallan Mishra
Feb 1, 2008·Annual Review of Pathology·Adriano AguzziMathias Heikenwaelder
Mar 18, 2008·Current Opinion in Chemical Biology·Kevin J Barnham, Ashley I Bush
Mar 25, 2008·Biochimica Et Biophysica Acta·Shankar J Chinta, Julie K Andersen
Aug 5, 2008·Molecular and Cellular Neurosciences·Jae-Min OhYong-Sun Kim
Nov 5, 2008·Journal of Medical Genetics·A GregoryS J Hayflick
Feb 3, 2009·Autophagy·Yasmine AguibAlexa Ertmer
Mar 14, 2009·PLoS Pathogens·Ajay SinghNeena Singh
May 5, 2009·Neurotoxicology·Pol Giménez-XavierSantiago Ambrosio
Oct 1, 2009·Physiological Reviews·Adriano Aguzzi, Anna Maria Calella

❮ Previous
Next ❯

Citations

Oct 12, 2012·Analytical and Bioanalytical Chemistry·Giuseppe Grasso, Giuseppe Spoto
Feb 19, 2013·Biochemical and Biophysical Research Communications·Bo-Ran ChoiHee-Jong Woo
Oct 11, 2015·Free Radical Biology & Medicine·Fabiana ZoleaFrancesco Costanzo
Jan 10, 2012·Biochemical and Biophysical Research Communications·Fernanda R BertuchiGiselle Cerchiaro
Feb 24, 2015·Frontiers in Cellular Neuroscience·Marcio H M da LuzKil S Lee
Jun 14, 2016·Parkinson's Disease·Yorka MuñozMarco T Núñez
Dec 12, 2012·Neurochemistry International·Claudia FunkeDouglas B Kell
Jan 13, 2015·The Journal of Biological Chemistry·Swati HaldarNeena Singh
Jan 13, 2017·PloS One·Vincenzo MatteiRoberta Misasi

❮ Previous
Next ❯

Methods Mentioned

BETA
Electron-microscopy
electron microscopy

Software Mentioned

GraphPad Prism
GraphPad

Related Concepts

Related Feeds

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.