Abstract
Mitochondrial dysfunction is a hallmark of beta-amyloid (Abeta)-induced neuronal toxicity in Alzheimer's disease (AD). Epidemiological studies have indicated that alcohol consumption plays a role in the development of AD. Here we show that alcohol exposure has a synergistic effect on Abeta-induced neuronal cell death. Abeta-treated cultured neurons displayed spontaneous generation of reactive oxygen species (ROS), disruption of their mitochondrial membrane potential, induction of caspase-3 and p53 activities, and loss of cell viability. Alcohol exposure facilitated Abeta-induced neuronal cell death. Our study shows that alcohol consumption enhances Abeta-induced neuronal cell death by increasing ROS and mitochondrial dysfunction.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / chemically induced*
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Alzheimer Disease / metabolism
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Amyloid beta-Peptides / metabolism*
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Amyloid beta-Peptides / pharmacology
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Apoptosis
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Cell Line, Tumor
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Ethanol / toxicity*
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Humans
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Membrane Potential, Mitochondrial / drug effects
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Membrane Potential, Mitochondrial / genetics
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Mitochondria / drug effects*
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Mitochondria / metabolism
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Neurons / cytology
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Neurons / drug effects*
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Neurons / metabolism
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Oligonucleotides, Antisense / genetics
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Oxidative Stress
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Peptide Fragments / metabolism*
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Peptide Fragments / pharmacology
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Proto-Oncogene Proteins c-akt / antagonists & inhibitors
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Proto-Oncogene Proteins c-akt / metabolism
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Reactive Oxygen Species / metabolism
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism
Substances
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Amyloid beta-Peptides
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Oligonucleotides, Antisense
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Peptide Fragments
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Reactive Oxygen Species
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Tumor Suppressor Protein p53
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amyloid beta-protein (1-42)
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Ethanol
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Proto-Oncogene Proteins c-akt