title: Thyroid hormone calorigenesis and mitochondrial redox signaling: upregulation of gene expression.
abstract: Thyroid hormone (TH, T3) is required for the normal function of most tissues, with major effects on O2 consumption and metabolic rate. These are due to transcriptional activation of respiratory genes through the interaction of T3-liganded TH receptors with TH response elements or the activation of intermediate factors, with the consequent higher rates of mitochondrial oxidative phosphorylation and reactive O2 species (ROS) generation and antioxidant depletion. The genomic effects of TH are accompanied by redox upregulation of the liver expression of cytokines (tumor necrosis factor-alpha [TNF-alpha]), enzymes (manganese superoxide dismutase), and anti-apoptotic proteins (Bcl-2), via a cascade initiated by TNF-alpha produced by Kupffer cells and involving inhibitor of kappa-B phosphorylation and nuclear factor-kappa-B activation. Thus, TH calorigenesis triggers non-genomic effects leading to an expression pattern that may represent an adaptive mechanism to re-establish redox homeostasis and promote cell survival under conditions of ROS toxicity secondary to TH-induced oxidative stress. Mechanisms of expression of respiratory and redox-sensitive genes may be functionally integrated, which could be of importance to understand the complexities of TH action and the outcome of thyroid gland dysfunction.
authors.affiliation: Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile. lvidela@med.uchile.cl
authors.forename: Luis A
authors.initials: LA
authors.lastname: Videla
authors.forename: Virginia
authors.initials: V
authors.lastname: Fernández
authors.forename: Gladys
authors.initials: G
authors.lastname: Tapia
authors.forename: Patricia
authors.initials: P
authors.lastname: Varela
mesh_terms: D000818:Animals; D004734:Energy Metabolism; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010101:Oxygen Consumption; D051381:Rats; D015398:Signal Transduction; D015533:Transcriptional Activation; D014284:Triiodothyronine / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D014284:Triiodothyronine