Juan Pablo Nicola
INTESTINAL Na+/I- SYMPORTER (NIS) EXPRESSION IS REGULATED AT POST-TRANSCRIPTIONAL LEVEL BY HIGH CONCENTRATIONS OF IODIDE Nicola JP (1), Susperreguy S (1), Carrasco N (2), Masini-Repiso AM (1)
(1) Centro de Investigaciones en Bioquímica Clínica e Inmunología. CIBICI-CONICET. Departamento de Bioquímica Clínica. Facultad de Ciencias Químicas. Universidad Nacional de Córdoba. Córdoba. Argentina. (2) Department of Molecular Pharmacology. Albert Einstein College of Medicine. NY. USA.
Dietary iodide absorption in the gastrointestinal tract constitutes the first step in iodide metabolism. Since this halogen is an essential component of the thyroid hormone, its concentrating mechanism is of considerable physiological importance. We have recently described and proposed the expression of the sodium/iodide symporter (NIS) on the apical surface of the intestinal epithelium as the central component of the iodide absorption system. The down-regulation of NIS by high iodide concentrations in the thyroid is related to the escape from Wolff-Chaikoff effect. The present study evaluated the effect of iodide excess on intestinal NIS expression and the mechanism involved using the small intestine cell line IEC-6. Cells treated with an excess of iodide reduced significantly the iodide uptake process which correlated in time with a diminution of NIS expression at the plasma membrane; however NIS reduction in the whole protein extract was delayed. NIS mRNA level was decreased by the treatment with high iodide doses. Surprisingly, no modulation on NIS promoter activity in transiently transfected IEC-6 cells was evidenced, suggesting a non transcriptional process. Evaluation of NIS protein and mRNA half-life showed that in the presence of iodide NIS protein half-life was slightly shortened whereas mRNA stability was strongly reduced. In conclusion, iodide excess down-regulates intestinal NIS function and expression as it was similarly observed in the thyroid. The effect of high iodide concentrations regulates NIS expression through a complex mechanism that involves regulation at different levels. Although premature, these results seem to indicate that a post-transcriptional regulation is exerted on NIS by high concentrations of its own substrate.