Linked Life Data

11152682

Source:http://linkedlifedata.com/resource/pubmed/id/11152682

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2001-4-3
pubmed:abstractText
The central event in prion disease is thought to be conformational conversion of the cellular isoform of prion protein (PrP(C)) to the insoluble isoform PrP(Sc). We generated polyclonal and monoclonal antibodies by immunizing PrP(C)-null mice with native PrP(C). All seven monoclonal antibodies (mAbs) immunoprecipitated PrP(C), but they immunoprecipitated PrP(Sc) weakly or not at all, thereby indicating preferential reactivities to PrP(C) in solution. Immunoprecipitation using these mAbs revealed a marked loss of PrP(C) in brains at the terminal stage of illness. Histoblot analyses using these polyclonal antibodies in combination of pretreatment of blots dissociated PrP(C) and PrP(Sc) in situ and consistently demonstrated the decrease of PrP(C) at regions where PrP(Sc) accumulated. Interestingly, same mAbs showed immunohistochemical reactivities to abnormal isoforms. One group of mAbs showed reactivity to materials that accumulated in astrocytes, while the other group did so to amorphous plaques in neuropil. Epitope mapping indicated that single mAbs have reactivities to multiple epitopes, thus implying dual specificities. This suggests the importance of octarepeats as a part of PrP(C)-specific conformation. Our observations support the notion that loss of function of PrP(C) may partly underlie the pathogenesis of prion diseases. The conversion of PrP(C) to PrP(Sc) may involve multiple steps at different sites.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11265-71
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
In vivo conversion of cellular prion protein to pathogenic isoforms, as monitored by conformation-specific antibodies.
pubmed:affiliation
National Institute of Animal Health, Tsukuba, Ibaraki 305-0856, Japan, Nippi Research Institute of Biomatrix, Adachi, Tokyo 120-8601, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't