Oxidative Stress Regulates the Activity of Nrf-2 Factor and the Transcription of Antioxidant Enzymes in Lymphoid Tissue of a Murine Model of Hyperthyroidism
Current Topics in Medicine and Medical Research Vol. 13,
29 April 2021
Hyperthyroidism is an endocrine disorder characterized by excessive secretion of triiodothyronine (T3) and thyroxine (T4). Thyroid hormones (THs) exert pleiotropic actions on numerous tissues and induce an overall increase in metabolism, with an increase in energy demand and oxygen consumption. Therefore, the purpose of this study was to investigate the effects of hyperthyroidism on the production of reactive oxygen species (ROS) in lymph node and spleen cells of euthyroid and hyperthyroid mice, analyzing antioxidant mechanisms involved in the restitution of the cellular redox state. For this, thirty female Balb/c mice were randomly divided into two groups: Euthyroid (by treatment with placebo) and Hyperthyroid (by treatment with 12 mg/l of T4 in drinking water for 30 days). We found a significant increase in ROS and an increase in the genomic and protein expression of the antioxidant enzymes Catalase (CAT) and Glutathione peroxidase-1 (GPx-1) in lymph node and spleen cells of hyperthyroid mice. In vitro treatment with H2O2 (250 ?M) of the lymphoid cells from euthyroid mice increased the expression of CAT and GPx-1. The hyperthyroidism increased the phosphorylation levels of Nrf-2 (Nuclear Factor Erythroid 2-related factor) and the kinase activity of Protein kinase C (PKC) and Extracellular signal-Regulated Kinase (ERK). Additionally, we found an increase in the expression of the classic isoenzymes of PKC?, ? and ?. The PKC and ERK kinases phosphorylated Nrf-2 and caused its translocation to the cell nucleus. In conclusion, these results indicated that the increase in ROS found in the lymphoid tissue of hyperthyroid mice induced the transcription of antioxidant enzymes through the activation of Nrf-2. We describe the molecular mechanisms involved in the regulation of the enzymatic antioxidant system in lymphoid cells of hyperthyroid mice. The knowledge about the modulation of the cellular redox state could be useful to establish new molecular targets for the treatment of pathologies associated with high levels of oxidative stress.
- oxidative stress
- antioxidants enzymes
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