DIFFERENT EFFECTS OF OXIDATIVE STRESS ON ACTIVATION OF TRANSCRIPTION FACTORS IN PRIMARY CULTURED RAT NEURONAL AND GLIAL-CELLS

We compared the cytotoxic effects of oxidative stress on neuronal and glial cells in vitro by examining the cell viability and changes in DN A-binding activities of transcription factors, AP-1 and CREB, using Tr ypan blue exclusion and electrophoretic mobility shift assay (EMSA), r espectively. Neurotoxin 6-hydroxydopamine (6-OHDA) and H2O2 reduced th e viability of both types of cells in time- and concentration-dependen t manner. Both neurotoxins dose-dependently decreased DNA-binding acti vities in neuronal cells. The results of cell viability assay suggeste d that these changes may reflect the reduction in neuronal cell viabil ity. In contrast, both reagents increased DNA-binding activities in gl ial cells, although they decreased cell numbers. These results suggest that the effects of oxidative stress on transcription factors is diff erent in neuronal and glial cells. We also examined the effect of brai n-derived neurotrophic factor (BDNF) on 6-OHDA- or H2O2-induced change s in DNA-binding activities. In neuronal cells, pre-treatment with BDN F prevented the decrease in DNA-binding activities induced by 6-OHDA o r H2O2. In glial cells, the effect of BDNF on oxidative stress-induced changes in DNA-binding activities in the 6-OHDA-treated group were op posite to those in H2O2-treated group. Our results suggest that 6-OHDA and H2O2 may exert their cytotoxic mechanisms through different signa l transduction systems. (C) 1997 Elsevier Science B.V.