Free radicals and lipid peroxidation do not mediate beta-amyloid-induced neuronal cell death.
"beta Amyloid (Abeta)-induced free radical-mediated neurotoxicity" is a leading hypothesis as a cause of Alzheimer's disease (AD). Abeta increased free radical production and lipid peroxidation in PC12 nerve cells, leading to increased 4-hydroxy-2-nonenal (HNE) production and modification of specific mitochondrial target proteins, apoptosis and cell death. Pretreatment of the cells with isolated ginkgolides, the anti-oxidant component of Ginkgo biloba leaves, or vitamin E, prevented the Abeta-induced increase of reactive oxygen species (ROS). Ginkgolides, but not vitamin E, inhibited the Abeta-induced HNE modification of mitochondrial proteins. However, treatment with these anti-oxidants did not rescue the cells from Abeta-induced apoptosis and cell death. These results indicate that free radicals and lipid peroxidation may not mediate Abeta-induced neurotoxicity.
Yao
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Division of Hormone Research, Departments of Cell Biology and Pharmacology, Georgetown University Medical Center, 3900 Reservoir Road, NW, Washington, DC 20007, USA.
Drieu
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Szweda
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Papadopoulos
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D000447:Aldehydes / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D004224:Diterpenes; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D046934:Ginkgolides; D007783:Lactones / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016716:PC12 Cells / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014810:Vitamin E / Q000494:pharmacology*
D000447:Aldehydes; D016229:Amyloid beta-Peptides; D004224:Diterpenes; D016166:Free Radical Scavengers; D005609:Free Radicals; D046934:Ginkgolides; D007783:Lactones; D017382:Reactive Oxygen Species; D014810:Vitamin E; C045856:ginkgolide B; C027576:4-hydroxy-2-nonenal