Linked Life Data

15686472

Source:http://linkedlifedata.com/resource/pubmed/id/15686472

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-2-2
pubmed:abstractText
Abstract Oxidative stress imparted by reactive oxygen species (ROS) is implicated in the pathogenesis of Alzheimer's disease (AD). Given that amyloid beta (Abeta) itself generates ROS that can directly damage proteins, elucidating the functional consequences of protein oxidation can enhance our understanding of the process of Abeta-mediated neurodegeneration. In this study, we employed a biocytin hydrazide/streptavidin affinity purification methodology followed by two-dimensional liquid chromatography tandem mass spectrometry coupled with SEQUEST bioinformatics technology, to identify the targets of Abeta-induced oxidative stress in cultured primary cortical mouse neurons. The Golgi-resident enzyme glucuronyltransferase (GlcAT-P) was a carbonylated target that we investigated further owing to its involvement in the biosynthesis of HNK-1, a carbohydrate epitope expressed on cell adhesion molecules and implicated in modulating the effectiveness of synaptic transmission in the brain. We found that increasing amounts of Abeta, added exogenously to the culture media of primary cortical neurons, significantly decreased HNK-1 expression. Moreover, in vivo, HNK-1 immunoreactivity was decreased in brain tissue of a transgenic mouse model of AD. We conclude that a potential consequence of Abeta-mediated oxidation of GlcAT-P is impairment of its enzymatic function, thereby disrupting HNK-1 biosynthesis and possibly adversely affecting synaptic plasticity. Considering that AD is partly characterized by progressive memory impairment and disordered cognitive function, the data from our in vitro studies can be reconciled with results from in vivo studies that have demonstrated that HNK-1 modulates synaptic plasticity and is critically involved in memory consolidation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
92
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
705-17
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:15686472-Amino Acid Sequence, pubmed-meshheading:15686472-Amyloid beta-Peptides, pubmed-meshheading:15686472-Animals, pubmed-meshheading:15686472-Antigens, CD57, pubmed-meshheading:15686472-Carbohydrate Conformation, pubmed-meshheading:15686472-Carbohydrate Sequence, pubmed-meshheading:15686472-Cells, Cultured, pubmed-meshheading:15686472-Down-Regulation, pubmed-meshheading:15686472-Female, pubmed-meshheading:15686472-Gene Expression Regulation, pubmed-meshheading:15686472-Glucuronosyltransferase, pubmed-meshheading:15686472-Mice, pubmed-meshheading:15686472-Mice, Transgenic, pubmed-meshheading:15686472-Molecular Sequence Data, pubmed-meshheading:15686472-Neural Cell Adhesion Molecules, pubmed-meshheading:15686472-Neurons, pubmed-meshheading:15686472-Oxidative Stress, pubmed-meshheading:15686472-Peptide Fragments, pubmed-meshheading:15686472-Pregnancy, pubmed-meshheading:15686472-Proteomics, pubmed-meshheading:15686472-Synaptic Transmission
pubmed:year
2005
pubmed:articleTitle
Reduced neuronal expression of synaptic transmission modulator HNK-1/neural cell adhesion molecule as a potential consequence of amyloid beta-mediated oxidative stress: a proteomic approach.
pubmed:affiliation
Department of Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't