High-density lipoprotein aggregated by oxidation induces degeneration of neuronal cells.
We have previously reported that high-density lipoprotein (HDL) exhibits antineuritogenic effects on chicken cerebral cells in culture. In the present study, we show the effects of HDLs, oxidized by UV irradiation or heating, on chicken cerebral neurons in culture. Both treatments produced several physical and chemical changes in the HDLs, i.e., formation of lipid peroxides, enlargement of HDL diameters, an increased exposure of the tryptophan groups of the apolipoprotein A-I to a more hydrophilic environment, formation of bityrosines, and cross-linking of apolipoprotein A-I. When these treatments were performed in the absence of EDTA, most of the modifications described above were more intense and HDLs formed a macroaggregate that displays a rosette-like structure. The aggregated HDLs produced neurodegeneration and death when added to both undifferentiated and differentiated cerebral neurons in culture. This process was accompanied by the disorganization of the cellular microtubular cytoskeleton and hyperphosphorylation of the microtubule-associated protein tau. Native HDL or HDLs treated in the presence of EDTA inhibited the neuritogenesis of undifferentiated neurons but did not show any significant effect on the differentiated neurons in culture. The effects on the cellular cytoskeleton and morphology of aggregated HDLs recall those of the fibrillar beta-amyloid peptide. The present results suggest that aggregated HDLs could participate in neurodegeneration associated with oxidative stress in the CNS.
Kivatinitz
S C
SC
Centro de Investigaciones en Química Biológica de Córdoba, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba/CONICET, Argentina.
Pelsman
M A
MA
Alonso
A C
AC
Bagatolli
L
L
Quiroga
S
S
D000818:Animals; D001921:Brain / Q000166:cytology / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D015227:Lipid Peroxidation / Q000187:drug effects*; D008075:Lipoproteins, HDL / Q000097:blood / Q000737:chemistry / Q000648:ultrastructure; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008870:Microtubules / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D009410:Nerve Degeneration; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009498:Neurotoxins; D010084:Oxidation-Reduction; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism*
D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D009498:Neurotoxins; C099252:oxidized low density lipoprotein; D016875:tau Proteins