title: Excess iodide induces an acute inhibition of the sodium/iodide symporter in thyroid male rat cells by increasing reactive oxygen species.
abstract: Na+/I- symporter (NIS) mediates iodide (I-) uptake in the thyroid gland, the first and rate-limiting step in the biosynthesis of the thyroid hormones. The expression and function of NIS in thyroid cells is mainly regulated by TSH and by the intracellular concentration of I-. High doses of I- for 1 or 2 days inhibit the synthesis of thyroid hormones, a process known as the Wolff-Chaikoff effect. The cellular mechanisms responsible for this physiological response are mediated in part by the inhibition of I- uptake through a reduction of NIS expression. Here we show that inhibition of I- uptake occurs as early as 2 hours or 5 hours after exposure to excess I- in FRTL-5 cells and the rat thyroid gland, respectively. Inhibition of I- uptake was not due to reduced NIS expression or altered localization in thyroid cells. We observed that incubation of FRTL-5 cells with excess I- for 2 hours increased H2O2 generation. Furthermore, the inhibitory effect of excess I- on NIS-mediated I- transport could be recapitulated by H2O2 and reverted by reactive derived oxygen species scavengers. The data shown here support the notion that excess I- inhibits NIS at the cell surface at early times by means of a posttranslational mechanism that involves reactive derived oxygen species.
authors.affiliation: Facultad de Ciencias Biológicas y Medicina (A.A.A., E.A., M.C.O., A.B., G.V., F.S., A.A.E., C.A.R.), Universidad Andrés Bello, República 217, Piso 4, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy (A.A.A., E.A., M.C.O., A.B., G.V., C.F., L.M., F.S., A.A.E., S.M.B., A.M.K., C.A.R.), Departamento de Endocrinología (C.F.) and Departamento de Reumatología (A.M.K.), Facultad de Medicina, and Departamento de Genética Molecular y Microbiología (S.M.B., A.M.K.), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8331010 Santiago, Chile; Center for Molecular Studies of the Cell (L.M.), ICBM, Facultad de Medicina, Universidad De Chile, 6640750 Santiago, Chile; Department of Cellular and Molecular Physiology (N.C.), Yale School of Medicine, New Haven, Connecticut 06520; and INSERM Unité Mixte de Recherche 1064 (S.M.B., A.M.K., C.A.R.), 44000 Nantes, France.
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Arriagada
authors.forename: Eduardo
authors.initials: E
authors.lastname: Albornoz
authors.forename: Ma Cecilia
authors.initials: MC
authors.lastname: Opazo
authors.forename: Alvaro
authors.initials: A
authors.lastname: Becerra
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Vidal
authors.forename: Carlos
authors.initials: C
authors.lastname: Fardella
authors.forename: Luis
authors.initials: L
authors.lastname: Michea
authors.forename: Nancy
authors.initials: N
authors.lastname: Carrasco
authors.forename: Felipe
authors.initials: F
authors.lastname: Simon
authors.forename: Alvaro A
authors.initials: AA
authors.lastname: Elorza
authors.forename: Susan M
authors.initials: SM
authors.lastname: Bueno
authors.forename: Alexis M
authors.initials: AM
authors.lastname: Kalergis
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Riedel
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006861:Hydrogen Peroxide / Q000378:metabolism; D007454:Iodides / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D027981:Symporters / Q000378:metabolism*; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000099209:Sodium-Iodide Symporters
chemical_list: D006861:Hydrogen Peroxide; D007454:Iodides; D017382:Reactive Oxygen Species; D027981:Symporters; D000099209:Sodium-Iodide Symporters