title: Nanomolar amyloid beta protein-induced inhibition of cellular redox activity in cultured astrocytes.
abstract: It has been previously reported that Alzheimer's amyloid beta protein (A beta) induces reactive astrocytosis in culture. In the present study, we found that A beta potently inhibits cellular redox activity of cultured astrocytes, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay. The following comparative studies revealed several differences between these two actions of A beta on astrocytes. First, A beta-induced reactive morphological change was suppressed by the presence of serum or thrombin, and A beta inhibition of cellular redox activity was observed in either the presence or the absence of serum. Second, micromolar concentrations (10 microM or more) were required for A beta to induce reactive astrocytosis, whereas nanomolar concentrations (0.1-100 nM) were sufficient to inhibit cellular redox activity. Third, the effect of micromolar A beta was virtually irreversible, but nanomolar A beta-induced inhibition of cellular redox activity was reversed by washing out A beta. Furthermore, as it has been reported that A beta neurotoxicity is mediated by reactive oxygen species, we also examined if similar mechanisms are involved in astrocytic response to A beta. However, neither A beta-induced morphological change nor inhibition of redox activity was blocked by antioxidants, suggesting that these effects are not caused by oxidative stress.
authors.affiliation: Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kato
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: K
authors.initials: K
authors.lastname: Abe
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D017382:Reactive Oxygen Species