title: Pendrin mediates uptake of perchlorate in a mammalian in vitro system.
abstract: Perchlorate is a known endocrine disruptor present in groundwater, vegetables and dairy food products in many regions of the United States. It interferes with the uptake of iodide into the thyrocyte by the sodium-iodide symporter at the basolateral surface, thus potentially disrupting the synthesis of thyroid hormone. Because transport of iodide from the thyroid follicular cells to the follicular lumen is mediated by the protein pendrin at the apical surface, we hypothesized that perchlorate may also interact with this protein. Therefore, HeLa cells were transfected with the human SLC26A4 gene, which encodes pendrin, to generate an in vitro mammalian system expressing the recombinant pendrin protein (HeLa-PDS). The HeLa-PDS cells, along with untransfected cells, were then cultured in presence of iodide and/or perchlorate. Intracellular levels of these two chemicals were measured by ion chromatography tandem mass spectrometry. Results from this study show that iodide and perchlorate uptake increases significantly in HeLa-PDS cells as compared to untransfected cells. Thus, recombinant HeLa cells expressing pendrin protein accumulate iodide and perchlorate intracellularly, indicating that pendrin is involved in the uptake of perchlorate. Additional results from this study suggest that iodide and perchlorate competitively inhibit each other for uptake by pendrin. The ability of perchlorate to compete with iodide for uptake by both basal and apical transporters may increase the potential of perturbation of thyroid homeostasis and therefore the estimated risk posed to susceptible human populations.
authors.affiliation: Department of Biology, Georgia State University, Atlanta, GA, USA. rattanasio@gsu.edu
authors.forename: Roberta
authors.initials: R
authors.lastname: Attanasio
authors.forename: Franco
authors.initials: F
authors.lastname: Scinicariello
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Blount
authors.forename: Liza
authors.initials: L
authors.lastname: Valentin-Blasini
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Rogers
authors.forename: Doan C
authors.initials: DC
authors.lastname: Nguyen
authors.forename: H Edward
authors.initials: HE
authors.lastname: Murray
mesh_terms: D000818:Animals; D052244:Endocrine Disruptors / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008322:Mammals / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D010472:Perchlorates / Q000378:metabolism*; D000076988:Sulfate Transporters
chemical_list: D052244:Endocrine Disruptors; D026901:Membrane Transport Proteins; D010472:Perchlorates; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; C494474:perchlorate