Linked Life Data

7970175

Source:http://linkedlifedata.com/resource/pubmed/id/7970175

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1994-12-29
pubmed:abstractText
Protein phosphorylation mediated by phorbol ester stimulates secretion of the beta-amyloid precursor protein (beta-APP) in the cell culture. This increase in secretion is produced by a transient increase in cleavage to produce non-amyloidogenic protease nexin II products mediated by the alpha-secretase activity, and a concomitant decrease in beta-protein production. Cells expressing the Swedish familial Alzheimer's disease (FAD) variant of beta-APP produce more beta-protein and potentially amyloidogenic fragments than cells expressing wild-type protein; furthermore, cleavage shifts from the alpha- to the beta-secretase cleavage site of the precursor. We show that treatment with phorbol 12,13-dibutyrate (PDBu) of cells expressing the Swedish FAD reverses the mutant phenotype to wild-type. The alpha-secretase cleavage increases with a concomitant loss of beta-protein and other beta-secretase cleaved products. These results show that modulating beta-secretase cleavage directly affects beta-protein production. It suggests that activating protein kinase C through, for example, muscarinic receptor agonists could reduce amyloidosis by modulating the level of beta-protein produced.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0304-3940
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
174
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
173-6
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Reversal of the Swedish familial Alzheimer's disease mutant phenotype in cultured cells treated with phorbol 12,13-dibutyrate.
pubmed:affiliation
CNS - Department of Biophysics and Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492.
pubmed:publicationType
Journal Article