| Cellular prion protein (PrPC) protects neuronal cells from the effect of huntingtin aggregation. | |
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MedLine Citation:
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PMID: 17635996 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The effect of normal cellular prion protein (PrP(C)) on abnormal protein aggregation was examined by transfecting huntingtin fragments (Htt) into SN56 neuronal-derived cells depleted of PrP(C) by RNA interference. PrP(C) depletion caused an increase in both the number of cells containing granules and the number of apoptotic cells. Consistent with the increase in Htt aggregation, PrP(C) depletion caused an decrease in proteasome activity and a decrease in the activities of cellular defense enzymes compared with control cells whereas reactive oxygen species (ROS) increased more than threefold. Therefore, PrP(C) may protect against Htt toxicity in neuronal cells by increasing cellular defense proteins, decreasing ROS and increasing proteasome activity thereby increasing Htt degradation. Depletion of endogenous PrP(C) in non-neuronal Caco-2 and HT-29 cells did not affect ROS levels or proteasome activity suggesting that only in neuronal cells does PrP(C) confer protection against Htt toxicity. The protective effect of PrP(C) was further evident in that overexpression of mouse PrP(C) in SN56 cells transfected with Htt caused a decrease in both the number of cells with Htt granules and the number of apoptotic cells, whereas there was no effect of PrP(C) expression in non-neuronal NIH3T3 or CHO cells. Finally, in chronically scrapie (PrP(Sc))-infected cells, ROS increased more than twofold while proteasome activity was decreased compared to control cells. Although this could be a direct effect of PrP(Sc), it is also possible that, since PrP(C) specifically prevents pathological protein aggregation in neuronal cells, partial loss of PrP(C) itself increases PrP(Sc) aggregation. |
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Authors:
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Kyung-Jin Lee; Antony Panzera; David Rogawski; Lois E Greene; Evan Eisenberg |
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Publication Detail:
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Type: Journal Article Date: 2007-07-17 |
Journal Detail:
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Title: Journal of cell science Volume: 120 ISSN: 0021-9533 ISO Abbreviation: J. Cell. Sci. Publication Date: 2007 Aug |
Date Detail:
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Created Date: 2007-07-24 Completed Date: 2007-12-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0052457 Medline TA: J Cell Sci Country: England |
Other Details:
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Languages: eng Pagination: 2663-71 Citation Subset: IM |
Affiliation:
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Laboratory of Cell Biology, NHBLI, NIH, Bethesda, MD 20892-0301, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line Cell Line, Tumor Humans Huntington Disease Mice Nerve Tissue Proteins / metabolism* Neurons / metabolism* Nuclear Proteins / metabolism Peptide Fragments / metabolism PrPC Proteins / metabolism* PrPSc Proteins / metabolism* Reactive Oxygen Species / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/HD protein, human; 0/Huntington protein, mouse; 0/Nerve Tissue Proteins; 0/Nuclear Proteins; 0/Peptide Fragments; 0/PrPC Proteins; 0/PrPSc Proteins; 0/Reactive Oxygen Species |
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