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

Recently, we demonstrated that 3,3,5-triiodothyronine (T3) induces oxidative stress in rat liver, with enhancement in the DNA binding of nuclear factorB (NFB) and the NFB-dependent expression of tumor necrosis factor(TNF). 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(ELISA), liver inhibitor of B (I B) phosphorylation (Western blot analysis), and hepatic NFB 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 -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 TNFrelease and activation of the I Bkinase/NFB cascade, which may constitute a protective mechanism against free radical toxicity involving cell death signaling. Journal of Endocrinology (2005) 186, 539–547