Redox up-regulated expression of rat liver manganese superoxide dismutase and Bcl-2 by thyroid hormone is associated with inhibitor of κB-α phosphorylation and nuclear factor-κB activation

Abstract

Recently, we demonstrated that 3,3′,5-triiodothyronine (T3) induces oxidative stress in rat liver, with enhancement in the DNA binding of nuclear factor-κB (NF-κB) and the NF-κB-dependent expression of tumor necrosis factor-α (TNF-α). In this study, we show that T3 administration (daily doses of 0.1 mg/kg i.p. for three consecutive days) elicited a calorigenic response and higher liver O₂ consumption rates, with increased serum levels of TNF-α (ELISA), liver inhibitor of κB (IκB-α) phosphorylation (Western blot analysis), and hepatic NF-κB DNA binding (EMSA) at 56–72 h after treatment. Within this time interval, liver manganese superoxide dismutase (MnSOD) activity and the protein expression of MnSOD and Bcl-2 are enhanced. These changes are abrogated by the administration of α-tocopherol (100 mg/kg i.p.) prior to T3. It is concluded that T3 treatment leads to the redox upregulation of MnSOD and Bcl-2 in rat liver, in association with TNF-α release and activation of the IκB-α kinase/NF-κB cascade, which may constitute a protective mechanism against free radical toxicity involving cell death signaling.