title: Opposing actions of native and oxidized lipoprotein on motor neuron-like cells.
abstract: Lipoproteins are present in the central nervous system and surrounding vasculature and possibly mediate effects relevant to neuronal physiology and pathology. To determine the effects of lipoproteins on motor neurons, native low density lipoproteins (LDL) and oxidized LDL (oxLDL) were applied to a motor neuron cell line. Oxidized LDL, but not native LDL, resulted in a dose- and time-dependent increase in reactive oxygen species and neuron death. Oxidized LDL-induced toxicity was attenuated by a calcium chelator, antioxidants, caspase inhibitors, and inhibitors of macromolecular synthesis. In addition to being nontoxic, application of native LDL attenuated reactive oxygen species formation and neuron loss following glucose deprivation injury. Together, these data demonstrate a possible neuroprotective role for unmodified lipoproteins and suggest oxidized lipoproteins may amplify oxidative stress and neuron loss.
authors.affiliation: Departments of Neurology and Pathology, University of Kentucky, Lexington, Kentucky 40536, USA.
authors.forename: J N
authors.initials: JN
authors.lastname: Keller
authors.forename: K B
authors.initials: KB
authors.lastname: Hanni
authors.forename: W A
authors.initials: WA
authors.lastname: Pedersen
authors.forename: N R
authors.initials: NR
authors.lastname: Cashman
authors.forename: M P
authors.initials: MP
authors.lastname: Mattson
authors.forename: S P
authors.initials: SP
authors.lastname: Gabbita
authors.forename: V
authors.initials: V
authors.lastname: Friebe
authors.forename: W R
authors.initials: WR
authors.lastname: Markesbery
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D061945:Caspase Inhibitors; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000172:deficiency; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D051379:Mice; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D061945:Caspase Inhibitors; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D008077:Lipoproteins, LDL; D011500:Protein Synthesis Inhibitors; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D012313:RNA; D005947:Glucose; D002118:Calcium