title: Influence of ZIP14 (slc39A14) on intestinal zinc processing and barrier function.
abstract: ZIP14 is a zinc transport protein with high expression in the small intestine and liver. Zip14 is upregulated during endotoxemia and leads to increased liver zinc content and transient hypozinemia. Since body zinc status and inflammation are associated with changes in intestinal permeability, we hypothesized that ZIP14 may influence intestinal permeability. Wild-type (WT) and Zip14 knockout (KO) mice were used to determine ZIP14-associated intestinal zinc metabolism and effects on permeability. Fractionation of plasma membranes revealed that ZIP14 is localized to the basolateral membrane of enterocytes. Studies utilizing (65)Zn administered by subcutaneous injection revealed greater zinc accumulation in the SI of Zip14 KO mice compared with WT mice. Isolation of endosomes confirmed the presence of ZIP14. Quantification of endosomal zinc concentration by FluoZin-3AM fluorescence demonstrated that zinc is trapped in endosomes of Zip14 KO mice. Intestinal permeability assessed both by plasma FITC-dextran following gavage and by serum endotoxin content was greater in Zip14 KO mice. Threonine phosphorylation of the tight junction protein occludin, which is necessary for tight junction assembly, was reduced in KO mice. Claudin 1 and 2, known to have an inverse relationship in regards to tight junction integrity, reflected impaired barrier function in KO jejunum. These data suggest involvement of ZIP14 in providing zinc for a regulatory role needed for maintenance of the intestinal barrier. In conclusion, ZIP14 is a basolaterally localized protein in enterocytes and is involved in endosomal trafficking of zinc and is necessary for proper maintenance of intestinal tight junctions.
authors.affiliation: Food Science and Human Nutrition Department and Center for Nutritional Sciences, College of Agricultural and Life Sciences, University of Florida, Gainesville, Florida.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Guthrie
authors.affiliation: Food Science and Human Nutrition Department and Center for Nutritional Sciences, College of Agricultural and Life Sciences, University of Florida, Gainesville, Florida.
authors.forename: Tolunay B
authors.initials: TB
authors.lastname: Aydemir
authors.affiliation: Food Science and Human Nutrition Department and Center for Nutritional Sciences, College of Agricultural and Life Sciences, University of Florida, Gainesville, Florida.
authors.forename: Catalina
authors.initials: C
authors.lastname: Troche
authors.affiliation: Food Science and Human Nutrition Department and Center for Nutritional Sciences, College of Agricultural and Life Sciences, University of Florida, Gainesville, Florida.
authors.forename: Alyssa B
authors.initials: AB
authors.lastname: Martin
authors.affiliation: Food Science and Human Nutrition Department and Center for Nutritional Sciences, College of Agricultural and Life Sciences, University of Florida, Gainesville, Florida.
authors.forename: Shou-Mei
authors.initials: SM
authors.lastname: Chang
authors.affiliation: Food Science and Human Nutrition Department and Center for Nutritional Sciences, College of Agricultural and Life Sciences, University of Florida, Gainesville, Florida cousins@ufl.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Cousins
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010539:Permeability; D019108:Tight Junctions / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*
chemical_list: D027682:Cation Transport Proteins; C500556:SLC39A14 protein, mouse; D015032:Zinc
keywords: endosomes; endotoxemia; intestinal permeability; mucosal defense; zinc transporter