Nanomolar amyloid beta protein-induced inhibition of cellular redox activity in cultured astrocytes.
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.
Kato
M
M
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Saito
H
H
Abe
K
K
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
D016229:Amyloid beta-Peptides; D017382:Reactive Oxygen Species