title: Dietary iodide controls its own absorption through post-transcriptional regulation of the intestinal Na+/I- symporter.
abstract: Dietary I(-) absorption in the gastrointestinal tract is the first step in I(-) metabolism. Given that I(-) is an essential constituent of the thyroid hormones, its concentrating mechanism is of significant physiological importance. We recently described the expression of the Na(+)/I(-) symporter (NIS) on the apical surface of the intestinal epithelium as a central component of the I(-) absorption system and reported reduced intestinal NIS expression in response to an I(-)-rich diet in vivo. Here, we evaluated the mechanism involved in the regulation of NIS expression by I(-) itself in enterocytes. Excess I(-) reduced NIS-mediated I(-) uptake in IEC-6 cells in a dose- and time-dependent fashion, which was correlated with a reduction of NIS expression at the plasma membrane. Perchlorate, a competitive inhibitor of NIS, prevented these effects, indicating that an increase in intracellular I(-) regulates NIS. Iodide induced rapid intracellular recruitment of plasma membrane NIS molecules and NIS protein degradation. Lower NIS mRNA levels were detected in response to I(-) treatment, although no transcriptional effect was observed. Interestingly, I(-) decreased NIS mRNA stability, affecting NIS translation. Heterologous green fluorescent protein-based reporter constructs revealed a significant repressive effect of the I(-)-targeting NIS mRNA 3 untranslated region. In conclusion, excess I(-) downregulates NIS expression in enterocytes by virtue of a complex mechanism. Our data suggest that I(-) regulates intestinal NIS mRNA expression at the post-transcriptional level as part of an autoregulatory effect of I(-) on its own metabolism.
authors.affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología-Consejo Nacional de Investigaciones Científicas y Técnicas (CIBICI-CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, X5000HUA, Córdoba, Argentina.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Nicola
authors.forename: Andrea
authors.initials: A
authors.lastname: Reyna-Neyra
authors.forename: Nancy
authors.initials: N
authors.lastname: Carrasco
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Masini-Repiso
mesh_terms: D000818:Animals; D002460:Cell Line; D004032:Diet; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D011193:Potassium Iodide / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters / Q000502:physiology*; D014158:Transcription, Genetic; D000099209:Sodium-Iodide Symporters
chemical_list: D011193:Potassium Iodide; D027981:Symporters; D000099209:Sodium-Iodide Symporters