Human, but not bovine, oxidized cerebral spinal fluid lipoproteins disrupt neuronal microtubules |
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Authors: | M D Neely L L Swift T J Montine |
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Affiliation: | (1) Department of Pathology, Medical Center North, Vanderbilt University, 1161 21st Street South, 37232-2561 Nashville, TN |
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Abstract: | Cerebral spinal fluid (CSF) lipoproteins have become a focus of research since the observation that inheritance of particular
alleles of the apolipoprotein E gene affects the risk of Alzheimer's disease (AD). There is evidence of increased lipid peroxidation
in CSF lipoproteins from patients with AD, but the biological significance of this observation is not known. A characteristic
of the AD brain is a disturbance of the neuronal microtubule organization. We have shown previously that 4-hydroxy-2(E)-nonenal, a major product of lipid peroxidation, causes disruption of neuronal microtubules and therefore tested whether
oxidized CSF lipoproteins had the same effect. We exposed Neuro 2A cells to human CSF lipoproteins and analyzed the microtubule
organization by immunofluorescence. In vitro oxidized human CSF lipoproteins caused disruption of the microtubule network, while their native (nonoxidized) counterparts
did not. Microtubule disruption was observed after short exposures (1 h) and lipoprotein concentrations were present in CSF
(20 μg/mL), conditions that did not result in loss of cell viability. Importantly, adult bovine CSF lipoproteins, oxidized
under identical conditions, had no effect on the microtubule organization of Neuro 2A cells. Comparison of human and bovine
CSF lipoproteins revealed similar oxidation-induced modifications of apolipoproteins E and A-I as analyzed by sodium dodecyl
sulfate-polyacrylamide gel electrophoresis and Western blotting. Fatty acid analysis revealed substantially lower amounts
of unsaturated fatty acids in bovine CSF lipoproteins, when compared to their human counterparts. Our data therefore indicate
that oxidized human CSF lipoproteins are detrimental to neuronal microtubules. This effect is species-specific, since equally
oxidized bovine CSF lipoproteins left the neuronal microtubule organization unchanged. |
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