title: Regulation of intracellular Zn homeostasis in two intestinal epithelial cell models at various maturation time points.
abstract: After weaning, piglets are often fed diets supplemented with high concentrations of zinc (Zn) to decrease post-weaning diarrhea. The aim of this study was to elucidate the regulation of Zn homeostasis within intestinal epithelial cells during excessive Zn exposure. High Zn concentrations elevated the intracellular Zn level in IPEC-J2 and Caco-2 cells which was influenced by differentiation status and time of exposure. With increasing Zn concentrations, mRNA and protein levels of metallothionein (MT) and zinc transporter 1 (ZnT1) were upregulated, whereas zinc transporter 4 (ZIP4) expression was downregulated. Metal-regulatory transcription factor-1 (MTF1) mRNA expression was upregulated at high Zn concentrations in IPEC-J2 cells, which corresponded to higher intracellular Zn concentrations. Based on these results, we suggest that intestinal epithelial cells adapt the expression of these genes to the amount of extracellular Zn available in order to maintain Zn homeostasis. Cell line-dependent differences in the regulation of Zn homeostasis were detected.
authors.affiliation: Department of Veterinary Medicine, Institute of Veterinary Physiology, Freie Universität Berlin, Oertzenweg 19b, 14163, Berlin, Germany.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Gefeller
authors.forename: Angelika
authors.initials: A
authors.lastname: Bondzio
authors.forename: Jörg R
authors.initials: JR
authors.lastname: Aschenbach
authors.forename: Holger
authors.initials: H
authors.lastname: Martens
authors.forename: Ralf
authors.initials: R
authors.lastname: Einspanier
authors.forename: Franziska
authors.initials: F
authors.lastname: Scharfen
authors.forename: Jürgen
authors.initials: J
authors.lastname: Zentek
authors.forename: Robert
authors.initials: R
authors.lastname: Pieper
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lodemann
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D042541:Intracellular Space / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034421:Sus scrofa; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015032:Zinc / Q000008:administration & dosage / Q000378:metabolism*; D000097809:Transcription Factor MTF-1
chemical_list: D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; D008668:Metallothionein; D012333:RNA, Messenger; D014157:Transcription Factors; D015032:Zinc; D000097809:Transcription Factor MTF-1; C530099:MT1A protein, human; C498299:SLC30A1 protein, human; C491597:SLC30A4 protein, human