Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2000-2-11
pubmed:abstractText
Brain regional oxidative damage is thought to be a central mechanism in the pathogenesis of Alzheimer's disease (AD). Recent studies of cerebrospinal fluid (CSF) have suggested that increased lipid peroxidation of CSF and CSF lipoproteins also may occur in AD patients. In the present study, we determined the susceptibility of human CSF to ex vivo lipid peroxidation and tested the hypothesis that oxidized CSF lipoproteins may be neurotoxic. Whole CSF or a CSF lipoprotein fraction (d < 1.210 g/mL) was oxidized with 2,2'-azobis(2-amidino-propane)dihydrochloride (AAPH), a hydrophilic free-radical generator. Kinetics of CSF lipid peroxidation were followed by a standard fluorescence product accumulation assay. Oxidation of AD CSF yielded significantly shorter fluorescent lag times than controls, indicating reduced antioxidant capacity. Electrophoretic mobilities of CSF apolipoproteins were specifically reduced upon oxidation of CSF with AAPH, suggesting that lipoproteins are primary targets of CSF lipid peroxidation. Cultured neuronal cells were exposed to physiological concentrations of isolated CSF lipoproteins oxidized with increasing concentrations of AAPH; the resulting neurotoxicity showed a significant linear AAPH concentration-response relationship. These results suggest that oxidized CSF lipoproteins may contribute to the pathogenesis of neurodegeneration in AD.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0024-4201
pubmed:author
pubmed:issnType
Print
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1273-80
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10652986-Aged, pubmed-meshheading:10652986-Alzheimer Disease, pubmed-meshheading:10652986-Amidines, pubmed-meshheading:10652986-Animals, pubmed-meshheading:10652986-Carbocyanines, pubmed-meshheading:10652986-Cell Line, pubmed-meshheading:10652986-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:10652986-Fatty Acids, pubmed-meshheading:10652986-Female, pubmed-meshheading:10652986-Free Radicals, pubmed-meshheading:10652986-Humans, pubmed-meshheading:10652986-Kinetics, pubmed-meshheading:10652986-Lipid Peroxidation, pubmed-meshheading:10652986-Lipid Peroxides, pubmed-meshheading:10652986-Male, pubmed-meshheading:10652986-Mice, pubmed-meshheading:10652986-Microscopy, Fluorescence, pubmed-meshheading:10652986-Neurotoxins, pubmed-meshheading:10652986-Spectrometry, Fluorescence
pubmed:year
1999
pubmed:articleTitle
Cerebrospinal fluid lipoproteins are more vulnerable to oxidation in Alzheimer's disease and are neurotoxic when oxidized ex vivo.
pubmed:affiliation
Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA. casey.bassett@mcmail.vanderbilt.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't