title: Beta-amyloid (1-42) affects MTT reduction in astrocytes: implications for vesicular trafficking and cell functionality.
abstract: Beta-amyloid (Abeta) peptide deposition in the brains of Alzheimer's disease patients results in reactive astrogliosis which may enhance neuronal cell death. Abeta has also been reported to impair important supportive astrocyte functions, such as glutamate uptake in vitro. We studied the effect of amyloid beta-peptide (Abeta) on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction, cellular ATP content, lactate release, and proliferation using neonatal rat astrocyte cultures. Abeta(1-42) decreased MTT reduction potently in the absence of cell death, but did not affect cellular ATP levels or lactate release. Moreover, the cells displayed increased proliferation after incubation with Abeta(1-42), confirming that the decreased MTT reduction was not deleterious to cell viability. Abeta(1-42) enhanced transfer of MTT dye to the cell surface leading to cessation of MTT reduction and cell death. Bafilomycin A1, but not brefeldin A, prevented the enhanced trafficking of MTT, suggesting that lysosomes, but not Golgi apparatus, are involved. Our results show that the viability of astrocytes themselves is not diminished by beta-amyloid peptide. However, Abeta alters vesicular trafficking in astrocytes, which may disturb the supportive function of astrocytes in the brains of patients with Alzheimer's disease.
authors.affiliation: Department of Neuroscience and Neurology, University of Kupio, Finland. petri.kerokoski@uku.fi
authors.forename: P
authors.initials: P
authors.lastname: Kerokoski
authors.forename: H
authors.initials: H
authors.lastname: Soininen
authors.forename: T
authors.initials: T
authors.lastname: Pirttilä
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000502:physiology; D001692:Biological Transport / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004396:Coloring Agents / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D007700:Kinetics; D010084:Oxidation-Reduction / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013778:Tetrazolium Salts / Q000378:metabolism*; D013844:Thiazoles / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D004396:Coloring Agents; D010446:Peptide Fragments; D013778:Tetrazolium Salts; D013844:Thiazoles; C075222:amyloid beta-protein (1-42); C022616:thiazolyl blue