Linked Life Data

8621605

Source:http://linkedlifedata.com/resource/pubmed/id/8621605

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
1996-6-18
pubmed:abstractText
The 4-kDa beta-amyloid peptide (Abeta), a principal component of parenchymal amyloid deposits in Alzheimer's disease, is derived from amyloid precursor proteins (APP). To identify potential intracellular compartments involved in Abeta production, we expressed human APP-695 (APPwt) and APP-695 harboring the Swedish double mutation (APPswe) associated with familial early-onset Alzheimer's disease, in mouse N2a cells. We demonstrate that cells expressing APPswe secrete high levels of Abeta peptides and beta-secretase-generated soluble APP derivatives (APP s beta) relative to cells expressing APPwt. In addition, we observed a concomitant diminution in the levels of alpha-secretase-generated soluble APP derivatives (APP s alpha). Our interpretation of these findings is that beta-secretase cleavage occurs in an intracellular compartment and disables those substrates which would normally be cleaved by alpha-secretase. As anticipated, the levels of APPswe are diminished relative to the steady-state levels of surface-bound APPwt; moreover, surface-bound APPswe and APPwt molecules are released from the plasma membrane after cleavage by alpha-secretase, but not by beta-secretase. Finally, by examining the rate of appearance of specific APP metabolites generated by beta-secretase, we now unequivocally demonstrate that beta-secretase cleavage of APPswe occurs within the Golgi apparatus, as early as the medial compartment.
pubmed:grant
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
19
pubmed:volume
271
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9390-7
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:8621605-Alzheimer Disease, pubmed-meshheading:8621605-Amino Acid Sequence, pubmed-meshheading:8621605-Amyloid Precursor Protein Secretases, pubmed-meshheading:8621605-Amyloid beta-Peptides, pubmed-meshheading:8621605-Amyloid beta-Protein Precursor, pubmed-meshheading:8621605-Animals, pubmed-meshheading:8621605-Aspartic Acid Endopeptidases, pubmed-meshheading:8621605-Cell Line, pubmed-meshheading:8621605-Cell Membrane, pubmed-meshheading:8621605-Endopeptidases, pubmed-meshheading:8621605-Genetic Variation, pubmed-meshheading:8621605-Golgi Apparatus, pubmed-meshheading:8621605-Humans, pubmed-meshheading:8621605-Kinetics, pubmed-meshheading:8621605-Mice, pubmed-meshheading:8621605-Models, Neurological, pubmed-meshheading:8621605-Molecular Sequence Data, pubmed-meshheading:8621605-Mutation, pubmed-meshheading:8621605-Neuroblastoma, pubmed-meshheading:8621605-Recombinant Proteins, pubmed-meshheading:8621605-Transfection, pubmed-meshheading:8621605-Tumor Cells, Cultured
pubmed:year
1996
pubmed:articleTitle
Metabolism of the "Swedish" amyloid precursor protein variant in neuro2a (N2a) cells. Evidence that cleavage at the "beta-secretase" site occurs in the golgi apparatus.
pubmed:affiliation
Department of Pathology, The John Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't