Linked Life Data

11835318

Source:http://linkedlifedata.com/resource/pubmed/id/11835318

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2002-2-8
pubmed:abstractText
Amyloid-beta peptide (Abeta) and the serpin proteinase inhibitor alpha1-antichymotrypsin (ACT) are components of the amyloid plaques associated with Alzheimer's disease (AD). Abeta exists in soluble monomeric and oligomeric forms and in an insoluble polymerised fibrillar form, but it is not clear which of these plays the most important role in the etiology of AD. In vitro, Abeta(1-42) interacts with ACT, and as a result of this, ACT loses its proteinase inhibitor activity and polymerisation of Abeta(1-42) is promoted. Here we provide evidence that new molecular forms resulting from incubation of ACT with Abeta(1-42) have multiple cellular level effects on neuronal cells. The mixture of soluble Abeta and an ACT/Abeta complex formed by 2 hr incubation at a 10:1 molar ratio of Abeta:ACT strongly induce cellular proliferation and expression of transcription factors peroxisome proliferator-activated receptor-gamma (PPARgamma) and NFkappaB, and also increase uptake and depress degradation of native and oxidised low-density lipoprotein (LDL) by cells. Similar but less pronounced effects are seen when cells are exposed to the Abeta peptide alone preincubated for 2 hr. Abeta(1-42) and to a lesser extent ACT/Abeta(1-42) complex mixture prepared by 2 hr incubation both inhibit association of native LDL with cells. Neither ACT alone nor the Abeta(1-42) and ACT/Abeta(1-42) forms prepared by 24-hr incubation show any significant effects in these assays. We propose that specific molecular forms of Abeta(1-42) and ACT/Abeta(1-42) complex mixture, both dependent on the abundances of Abeta(1-42) and ACT/Abeta(1-42) in vivo and on their time of exposure to each other, have cellular effects which are important for the initiation and progression of the pathologies associated with AD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0360-4012
pubmed:author
pubmed:copyrightInfo
Copyright 2002 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
511-22
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:11835318-Alzheimer Disease, pubmed-meshheading:11835318-Amyloid beta-Peptides, pubmed-meshheading:11835318-Binding Sites, pubmed-meshheading:11835318-Brain, pubmed-meshheading:11835318-Cell Division, pubmed-meshheading:11835318-Electrophoresis, pubmed-meshheading:11835318-Gene Expression Regulation, pubmed-meshheading:11835318-Humans, pubmed-meshheading:11835318-Lipid Metabolism, pubmed-meshheading:11835318-Lipoproteins, LDL, pubmed-meshheading:11835318-NF-kappa B, pubmed-meshheading:11835318-Neuroblastoma, pubmed-meshheading:11835318-Neurons, pubmed-meshheading:11835318-Oxidation-Reduction, pubmed-meshheading:11835318-Peptide Fragments, pubmed-meshheading:11835318-Plaque, Amyloid, pubmed-meshheading:11835318-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:11835318-Transcription, Genetic, pubmed-meshheading:11835318-Transcription Factors, pubmed-meshheading:11835318-Tumor Cells, Cultured, pubmed-meshheading:11835318-alpha 1-Antichymotrypsin
pubmed:year
2002
pubmed:articleTitle
Alpha1-antichymotrypsin/Alzheimer's peptide Abeta(1-42) complex perturbs lipid metabolism and activates transcription factors PPARgamma and NFkappaB in human neuroblastoma (Kelly) cells.
pubmed:affiliation
Department of Medicine, Wallenberg Laboratory, University Hospital Malmö, S-20502 Malmö, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't