Oxidative Stress Produced by Hyperthyroidism Status Induces the Antioxidant Enzyme Transcription through the Activation of the Nrf-2 Factor in Lymphoid Tissues of Balb/c Mice

Scheme 1

Transduction signals in lymphocytes involved in the regulation of oxidative stress induced by hyperthyroidism. Hyperthyroidism is characterized by increased levels of circulating T3 and T4. The excess of thyroid hormones in lymphoid cells induces an increase in oxidative stress that leads to the oxidation of numerous proteins, including Keap-1. Under euthyroid conditions the Keap-1 dimer binds to Nrf-2. This interaction induces the ubiquitination of Nrf-2 and its consequent degradation in the proteasome; therefore, the levels of this factor are diminished in the cytoplasm. However, under hyperthyroid conditions, the reactive oxygen species oxidize the sulfhydryl groups of Keap-1/Nrf-2 complex. In this way, free Nrf-2 can be phosphorylated by PKC and ERK, two kinases that increase their activity in the hyperthyroid state. Phosphorylated Nrf-2 translocates to the cell nucleus and activates the transcription of antioxidant enzyme genes. The increased expression of antioxidant enzymes contributes to diminish the levels of oxidative stress generated by hyperthyroid conditions.