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 (T-3). 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 It and 120 h of treatment. In general, catalase and GPx-1 showed opposite responses in both transcription and translation. T-3 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 T-3 at multiple levels. Reduced and oxidized glutathione were depleted in hyperthyroid rats. Though T-3 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. (C) 2007 Elsevier Inc. All rights reserved.