Redox up-regulated expression of rat liver manganese superoxide dismutase and Bcl-2 by thyroid hormone is associated with inhibitor of kappaB-alpha phosphorylation and nuclear factor-kappaB activation.
Recently, we demonstrated that 3,3',5-triiodothyronine (T3) induces oxidative stress in rat liver, with enhancement in the DNA binding of nuclear factor-kappaB (NF-kappaB) and the NF-kappaB-dependent expression of tumor necrosis factor-alpha (TNF-alpha). 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-alpha (ELISA), liver inhibitor of kappaB (IkappaB-alpha) phosphorylation (Western blot analysis), and hepatic NF-kappaB 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 alpha-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-alpha release and activation of the IkappaB-alpha kinase/NF-kappaB cascade, which may constitute a protective mechanism against free radical toxicity involving cell death signaling.
Fernández
Virginia
V
Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Casilla, Santiago. vfernand@med.uchile.cl
Tapia
Gladys
G
Varela
Patricia
P
Castillo
Iván
I
Mora
Catalina
C
Moya
Francisco
F
Orellana
Myriam
M
Videla
Luis A
LA
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D020672:I-kappa B Proteins / Q000378:metabolism*; D007118:Immunoassay / Q000379:methods; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010084:Oxidation-Reduction; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism*; D051996:Transcription Factor RelA; D014284:Triiodothyronine / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D024502:alpha-Tocopherol / Q000494:pharmacology
D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D014284:Triiodothyronine; D000072000:NF-KappaB Inhibitor alpha; D013482:Superoxide Dismutase; D024502:alpha-Tocopherol