Alcohol enhances Abeta42-induced neuronal cell death through mitochondrial dysfunction

• Published in: FEBS letters 2008-12, Vol.582 (30), p.4185
• Main Authors: Lee, Do Yeon, Lee, Kyu-Sun, Lee, Hyun Jung, Jung, Hee-Yeon, Lee, Jun Young, Lee, Sang Hyung, Youn, Young Chul, Seo, Kyung Mook, Lee, Jang Han, Lee, Won Bok, Kim, Sung Su
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - chemically induced; Alzheimer Disease - metabolism; Amyloid beta-Peptides - metabolism; Amyloid beta-Peptides - pharmacology; Apoptosis; Cell Line, Tumor; Ethanol - toxicity; Humans; Membrane Potential, Mitochondrial - drug effects; Membrane Potential, Mitochondrial - genetics; Mitochondria - drug effects; Mitochondria - metabolism; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Oligonucleotides, Antisense - genetics; Oxidative Stress; Peptide Fragments - metabolism; Peptide Fragments - pharmacology; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; Reactive Oxygen Species - metabolism; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism
• ISSN: 1873-3468
• DOI: 10.1016/j.febslet.2008.11.007

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.