Linked Life Data

11750072

Source:http://linkedlifedata.com/resource/pubmed/id/11750072

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-12-25
pubmed:abstractText
The underlying neurochemical changes contributing to prion-induced neurodegeneration remain largely unknown. This study shows that scrapie infection induced a 2-fold increase of insulin receptor (IR) protein and aberrantly processed IR beta-chain in scrapie-infected N2a neuroblastoma cells (ScN2a) as measured by Western blot of immunoprecipitated IR, in the absence of increased IR mRNA. Elevated IR protein level was further confirmed in an independently scrapie-infected neuroblastoma cell line N1E-115 (ScN1E-115). Proliferation studies showed that the increased IR level in ScN2a did not result in an increased insulin-mediated cell growth compared to normal N2a cells. Binding studies indicated that this apparent paradox was due to a 65% decrease in specific [(125)I]insulin binding sites in ScN2a when compared to the amount of immunoreactive IR, although the IR binding affinity was unchanged. Analysis of insulin stimulated IR tyrosine phosphorylation showed a slight but not significant reduction in ScN2a, when related to the increased level of immunoreactive IR. However, comparing the IR tyrosine phosphorylation to the loss of binding sites in ScN2a, we demonstrated an increased IR tyrosine phosphorylation of the remaining functional IR. In addition to these differences in IR properties, the basal extracellular signal regulated kinase-2 (ERK2) phosphorylation detected by Western blot, was significantly elevated and the insulin stimulated ERK2 phosphorylation was subsequently decreased in ScN2a. Together, these data show that scrapie infection affects the level and processing of the IR and signal transduction mediated by the IR in neuroblastoma cells, as well as induces an elevated basal ERK2 phosphorylation. Aberrant regulation of neuroprotective receptors may contribute to neurodegeneration in prion diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0169-328X
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
97
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
161-70
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Altered insulin receptor processing and function in scrapie-infected neuroblastoma cell lines.
pubmed:affiliation
Department of Neurochemistry and Neurotoxicology, University of Stockholm, Svante Arrhenius v. 21A, S-10691 Stockholm, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't