Linked Life Data

15694266

Source:http://linkedlifedata.com/resource/pubmed/id/15694266

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-2-7
pubmed:abstractText
In the processing of APP, alpha- and beta-secretase pathways compete with each other for cleaving APP. Therefore, physiologically these two secretases are likely to colocalize in the same subcellular compartments. Previously beta-secretase cleavage of APP was found in the endoplasmic reticulum (ER). We herein tested whether alpha-secretase cleavage is also detected in the ER. We used experimental system of COS7 cells transfected with cDNA encoding human APP695, and the cell lysates and media were examined for its proteolytic products. When APP expression is concentrated in the ER by BFA-mediated transport inhibition or by using mutant APP harboring an ER-retrieval motif, alpha-secretase product sAPPalpha was accumulated in the cells. Immunofluorescence microscopy revealed that the ER-targeted APP produced intracellular accumulation of sAPPalpha, colocalizing with an ER marker. These results indicate that alpha-secretase cleavage of APP occurs in the ER. Further we examined the effects of phorbol ester PDBu, a direct activator of PKC, on the alpha-secretase and beta-secretase cleavages of APP occurring in the ER. Treatment with PDBu of COS7 cells transfected with the ER-targeted APP increased production of sAPPalpha and conversely decreased production of beta-secretase product sAPPbeta. Thus, in the ER, alpha-secretase competes with beta-secretase for cleaving APP and such competitive correlation might modulate the production of Abeta42 found in this compartment.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0304-3940
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
376
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
14-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15694266-Amyloid Precursor Protein Secretases, pubmed-meshheading:15694266-Amyloid beta-Protein Precursor, pubmed-meshheading:15694266-Animals, pubmed-meshheading:15694266-Aspartic Acid Endopeptidases, pubmed-meshheading:15694266-Blotting, Western, pubmed-meshheading:15694266-Brefeldin A, pubmed-meshheading:15694266-COS Cells, pubmed-meshheading:15694266-Cercopithecus aethiops, pubmed-meshheading:15694266-Endopeptidases, pubmed-meshheading:15694266-Endoplasmic Reticulum, pubmed-meshheading:15694266-Enzyme Activation, pubmed-meshheading:15694266-Humans, pubmed-meshheading:15694266-Immunohistochemistry, pubmed-meshheading:15694266-Peptide Fragments, pubmed-meshheading:15694266-Phorbol 12,13-Dibutyrate, pubmed-meshheading:15694266-Protein Synthesis Inhibitors, pubmed-meshheading:15694266-Subcellular Fractions, pubmed-meshheading:15694266-Transfection
pubmed:year
2005
pubmed:articleTitle
Novel alpha-secretase cleavage of Alzheimer's amyloid beta precursor protein in the endoplasmic reticulum of COS7 cells.
pubmed:affiliation
Department of Neurological Science, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Sendai 980-8575, Japan. shin@mail.tains.tohoku.ac.jp
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't