The influence of oxidative stress on catalase and MnSOD gene transcriptionin astrocytes

The brain is particularly vulnerable to oxygen free radicals, which have be en implicated in the pathology of several neurological disorders. The antio xidant enzyme (AOE) system of the brain may play an important role in the p rotection against such oxidative stress. We investigated the influence of o xidative stress on the transcription of catalase and MnSOD mRNA. Primary ra t astroglial cell cultures were treated either with hydrogen peroxide (H2O2 ), as a direct mediator of oxidative stress, or with the redox cycling comp ound paraquat. Both substances led to an increase of catalase and MnSOD mRN A levels. To further elucidate the mechanisms residing behind this increase , transfection experiments were performed. Transient transfection of primar y astroglial cells with a reporter plasmid containing the upstream region o f the catalase gene showed a decrease in reporter gene activity after expos ure of transfected cells to either H2O2 or paraquat. In contrast, transfect ion experiments done with reporter plasmids for the MnSOD upstream region r esulted in an increase of reporter gene activity after H2O2 as well as afte r paraquat treatment of transfected cells. These results indicate transcrip tional regulation of MnSOD and post-transcriptional regulation of catalase gene expression after oxidative stress in primary rat astrocytes. (C) 2001 Elsevier Science B.V. All rights reserved.