Alcohol enhances Abeta42-induced neuronal cell death through mitochondrial dysfunction.
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.
Lee
Do Yeon
DY
Department of Anatomy and Cell biology, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea.
Lee
Kyu-Sun
KS
Lee
Hyun Jung
HJ
Jung
Hee-Yeon
HY
Lee
Jun Young
JY
Lee
Sang Hyung
SH
Youn
Young Chul
YC
Seo
Kyung Mook
KM
Lee
Jang Han
JH
Lee
Won Bok
WB
Kim
Sung Su
SS
D000544:Alzheimer Disease / Q000139:chemically induced* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D000431:Ethanol / Q000633:toxicity*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000235:genetics; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000235:genetics; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016376:Oligonucleotides, Antisense; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C075222:amyloid beta-protein (1-42); D000431:Ethanol; D051057:Proto-Oncogene Proteins c-akt