Differential expression profiles of antioxidant enzymes and glutathione redox status in hyperthyroid rats: A temporal analysis

Our objective was to elucidate a temporal profile of expression of antioxidant enzymes (AOEs) and glutathione redox status in rat liver under the influence of thyroid hormone (T3). The key AOEs, superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx-1) and glutathione reductase (GR) were characterized at transcriptional, translational and biochemical levels after 24 h, 72 h and 120 h of treatment. In general, catalase and GPx-1 showed opposite responses in both transcription and translation. T3 treatment caused tightly coordinated downregulation of catalase. However, transcriptional changes of other AOEs over the different durations of treatment were not always reflected in their respective protein and/or activity levels. Discordance among transcripts, proteins and biological activities of AOEs suggested differential regulation by T3 at multiple levels. Reduced and oxidized glutathione were depleted in hyperthyroid rats. Though T3 exerted a positive stimulatory effect on glucose-6-phosphate dehydrogenase, it was not sufficient to compensate for massive glutathione depletion and impaired activities of GPx-1, GR and GST, disturbing the cellular redox status in the process. Apparently, while transcriptional induction of AOEs might be adaptive responses in conditions of oxidative stress, yet post-transcriptional regulation appeared to be the predominant mechanism of regulation of AOE expression.