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The Na + /I − symporter (NIS) mediates electroneutral active transport of the environmental pollutant perchlorate

2007; National Academy of Sciences; Volume: 104; Issue: 51 Linguagem: Inglês

10.1073/pnas.0707207104

1091-6490

Orsolya Dohán, Carla Portulano, Cécile Basquin, Andrea Reyna‐Neyra, L. Mario Amzel, Nancy Carrasco,

Water Treatment and Disinfection

The Na + /I − symporter (NIS) is a key plasma membrane protein that mediates active I − uptake in the thyroid, lactating breast, and other tissues with an electrogenic stoichiometry of 2 Na + per I − . In the thyroid, NIS-mediated I − uptake is the first step in the biosynthesis of the iodine-containing thyroid hormones, which are essential early in life for proper CNS development. In the lactating breast, NIS mediates the translocation of I − to the milk, thus supplying this essential anion to the nursing newborn. Perchlorate (ClO 4 − ) is a well known competitive inhibitor of NIS. Exposure to food and water contaminated with ClO 4 − is common in the U.S. population, and the public health impact of such exposure is currently being debated. To date, it is still uncertain whether ClO 4 − is a NIS blocker or a transported substrate of NIS. Here we show in vitro and in vivo that NIS actively transports ClO 4 − , including ClO 4 − translocation to the milk. A simple mathematical fluxes model accurately predicts the effect of ClO 4 − transport on the rate and extent of I − accumulation. Strikingly, the Na + / ClO 4 − transport stoichiometry is electroneutral, uncovering that NIS translocates different substrates with different stoichiometries. That NIS actively concentrates ClO 4 − in maternal milk suggests that exposure of newborns to high levels of ClO 4 − may pose a greater health risk than previously acknowledged because ClO 4 − would thus directly inhibit the newborns' thyroidal I − uptake.