Linked Life Data

8077213

Source:http://linkedlifedata.com/resource/pubmed/id/8077213

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
36
pubmed:dateCreated
1994-10-4
pubmed:abstractText
The amyloid beta-protein (A beta) and protease nexin-2/amyloid beta-protein precursor (PN-2/A beta PP) are major constituents of senile plaques and cerebrovascular deposits in individuals with Alzheimer's disease and related disorders. It has been suggested that the coagulation protease thrombin may process A beta PP in a manner leading to the formation of A beta. Here we investigated the effects of thrombin on the secretion and processing of PN-2/A beta PP and the production of A beta in a cellular system. Incubation of glioblastoma cells with thrombin (1-5 nM) resulted in the accumulation of abnormally processed, carboxyl-terminal-truncated forms of secreted PN-2/A beta PP (approximately 85 kDa) in the culture medium. Higher concentrations of thrombin (> 10 nM) also increased the levels of secreted PN-2/A beta PP in cultured untransfected glioblastoma cells and glioblastoma cells that were stably transfected to overproduce the 695 isoform of A beta PP. Increased secretion of PN-2/A beta PP required the proteolytic activity of thrombin, was induced by activation of the thrombin receptor by agonist peptides, and required activation of protein kinase C. Incubation of the untransfected and transfected glioblastoma cells with thrombin led to decreased levels of soluble A beta in the culture medium consistent with previously suggested mechanisms regarding the secretion of PN-2/A beta PP. Although the present studies suggest that thrombin does not directly contribute to A beta formation, its proteolysis of secreted PN-2/A beta PP may disrupt regions near the carboxyl terminus of the secreted proteins that account for their neuroprotective and cell adhesive properties.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
269
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
22623-7
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Thrombin receptor activation induces secretion and nonamyloidogenic processing of amyloid beta-protein precursor.
pubmed:affiliation
Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine 92717-4025.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't