Hepcidin attenuates zinc efflux in Caco‐2 cells
Abstract
Hepcidin, a peptide hormone produced by theliver in response to iron loading and inflammation, regulates body iron storesby inhibiting iron transporter function. Zinc also regulates hepcidinexpression; however, the effects of hepcidin on zinc transport and zinctransporter function have not been documented. The objective of this study wasto determine whether hepcidin affects intestinal zinc transport. Differentiatedhuman intestinal Caco‐2 cells were treated ± 1μM hepcidin for 3–24 h. Zinctransport was assessed in cells seeded on Transwell inserts. Media was collected from the apical and basolateral chambers and 67Znconcentrations were determined by ICP‐MS. Expression of metallothionein (MT1A), ZIP4 (SLC39A4), and ZnT1 (SLC30A1)was determined using RT‐qPCR and Western blot. Hepcidin attenuated zinctransport, as cells treated with hepcidin exported 20 and 26% less 67Zninto the basolateral chamber at 3 h and 24 h (P67Zn(PPPP>0.05), whereas hepcidin reduced ZnT1 protein by 75% (P<0.05) as compared to control cells. These data suggest that hepcidin is a regulatory hormone that manages zinc transport in intestinal cells by downregulating ZnT1 to reduce zinc export and increasing metallothionein to buffer the rise in intracellular zinc. Understanding the mechanism and role of hepcidin in zinc homeostasis may provide insight into the hypozincemiaassociated with inflammation and infection.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2016
- Source ID
- 10.1096/fasebj.30.1_supplement.292.3
Entities
People
- James P. Mcclung
- Stephen R Hennigar
Organizations
- United States Army Medical Research and Development Command