Oxidized low density lipoprotein caused CNS neuron cell death.
Death induced by oxidized low density lipoproteins (oxLDL) to embryonic CNS neuronal and neuroblastoma cells was investigated. Cell damage and viability were evaluated by LDH leakage and the MTT method, respectively. Dose- and time-dependent degeneration of neurons occurred after oxLDL (1-100 microg/ml) treatment but was absent after native low density lipoproteins (LDL). This degeneration was mediated, in part, by apoptosis because increased TUNEL and Hoechst dye-positive staining was observed. These effects occurred in the absence of microglia. However, DNA degradation was not detected. The cytotoxicity was attenuated by pre-treatment with antioxidants. These results suggest that oxidation by oxLDL may be important in neurocytotoxicity in the brain.
Sugawa
M
M
Fuji-Gotemba Research Laboratories Chugai Pharmaceutical Co. Ltd., Gotemba-shi, Shizuoka, Japan. sugawamkt@gt.chugai-pharm.co.jp
Ikeda
S
S
Kushima
Y
Y
Takashima
Y
Y
Cynshi
O
O
D000818:Animals; D000931:Antidotes / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001710:Biotin; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D003545:Cysteine / Q000494:pharmacology; D053938:DNA Fragmentation; D003856:Deoxyuracil Nucleotides; D004229:Dithiothreitol / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000166:cytology; D005978:Glutathione / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000494:pharmacology*; D009447:Neuroblastoma; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014810:Vitamin E / Q000494:pharmacology
D000931:Antidotes; D000975:Antioxidants; D003856:Deoxyuracil Nucleotides; D008077:Lipoproteins, LDL; D013439:Sulfhydryl Reagents; D017392:Thiobarbituric Acid Reactive Substances; C099252:oxidized low density lipoprotein; D014810:Vitamin E; D001710:Biotin; D005978:Glutathione; D003545:Cysteine; D004229:Dithiothreitol