| Translocation of cellular prion protein to non-lipid rafts protects human prion-mediated neuronal damage. | |
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MedLine Citation:
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PMID: 22179431 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Prions are the causative agents of transmissible spongiform encephalopathies, such as variant Creutzfeldt-Jakob disease in humans. Cellular prion proteins (PrPC) connect with cholesterol- and glycosphingolipid-rich lipid rafts through association of their glycosyl-phosphatidylinositol (GPI) anchor with saturated raft lipids and interaction of their N-terminal regions. Our previous study showed that cellular cholesterol enrichment prevented PrP(106-126)-induced neuronal death. We have now studied the influence of membrane cholesterol in PrP(106-126)-mediated neurotoxicity and identified membrane domains involved in this activity. We found that PrPC is normally distributed in lipid rafts, but high membrane cholesterol levels as a result of cholesterol treatment led to the translocation of PrPC from lipid rafts to non-lipid rafts. Moreover, cholesterol-mediated PrPC translocation protects PrP(106-126)-mediated apoptosis and p-38 activation and caspase-3 activation. In a mitochondrial functional assay including mitochondrial transmembrane potential, cholesterol treatment prevented the loss of mitochondrial potential, translocation of Bax and cytochrome c by prion protein fragment. Our results indicate that modulation of the PrPC location appears to protect against neuronal cell death caused by prion peptides. The results of this study suggest that regulation of membrane cholesterol affects the translocation of PrPC, which in turn regulates PrP(106-126)-induced mitochondrial dysfunction and neurotoxicity. |
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Authors:
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Jae-Kyo Jeong; Myung-Hee Moon; You-Jin Lee; Jae-Won Seol; Sang-Youel Park |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-15 |
Journal Detail:
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Title: International journal of molecular medicine Volume: - ISSN: 1791-244X ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-19 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9810955 Medline TA: Int J Mol Med Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Korea Zoonoses Research Institute, Center for Healthcare Technology Development, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, Republic of Korea. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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