Thioredoxin reductase and glutathione synthesis is upregulated by t-butylhydroquinone in cortical astrocytes but not in cortical neurons

The electron donors glutathione and thioredoxin play many vital roles in th e mechanisms of cells to cope with oxidative stress. Critical to such antio xidant functions are the ability to synthesize glutathione and keep it redu ced via glutathione reductase and the ability to reduce oxidized-thioredoxi n via thioredoxin reductase. The rate-limiting enzyme for glutathione synth esis, gamma-glutaamylcysteine synthase, is regulated by the antioxidant res ponse element, whereas little is known about the regulation of expression o f the selenoenzyme thioredoxin reductase. There were several objectives in this study. One was to determine whether the phase II enzyme inducer t-buty lhydroquinone would increase thioredaxin reductase in neural cells; we foun d that both cytosolic and mitochondrial thioredoxin reductase activity and protein content is increased in cortical astrocytes, but not in cortical ne urons. A second objective was to determine whether there are differences in the ability oft-butylhydroquinone to increase glutathione content in astro cytes and neurons; we found that glutathione is increased in astrocytes but not neurons. Finally, t-butylhydroquinone addition did not affect glutathi one reductase activity in neurons and caused only a modest increase in astr ocytes. Our findings emphasize the central role that astrocytes play in the antioxidant activities of the CNS. Our findings also suggest that thioredo xin reductase and gamma-glutamylcysteine synthase belong to the same synexp ression group. (C) 2000 Wiley-Liss, Inc.