Effects of Hepcidin on Zinc Homeostasis in HepG2 cells
Abstract
Hepcidin, a peptide hormone produced by theliver in response to iron loading and inflammation, regulates body iron storesby inhibiting iron transporter function. Recently, hepcidin was shown toinhibit zinc efflux in intestinal epithelial cells. The objective of this study was to determine whether hepcidin affects hepatic zinc homeostasis. Human HepG2cells were treated ± 1μM hepcidin for 24 h. Labile zinc pools were labeled with the zinc‐specific fluoroionophore FluoZin‐3‐AM (Kd 15 nM) and visualized and quantified using confocal microscopy and a fluorescent platereader. Expression of metallothionein, ZIP14, and ZnT1 was determined by Western blot. Intracellular zinc in control cells was localized to vesiclesdispersed throughout the cytoplasm; however, the number of vesicles and intensity of FluoZin‐3 fluorescence decreased by 38% in cells treated with hepcidin for 24 h (34.0 ± 11.3 and 21.0 ± 11.2 RFU/OD 562 nm; P0.05), whereas hepcidin increased ZnT1 expression (P<0.05) as compared to control cells. These data suggest that hepcidin may affect zinc homeostasis in liver cells. Understanding the mechanism and role of hepcidin in zinc homeostasis may provide insight in to the hypozincemia associated with inflammation and infection.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2017
- Source ID
- 10.1096/fasebj.31.1_supplement.802.4
Entities
People
- Alyssa M. Kelley
- James P. Mcclung
- Stephen R Hennigar
Organizations
- Oak Ridge Institute for Science and Education
- United States Army Medical Research and Development Command
- United States Army Research Institute of Environmental Medicine
- United States Department of Defense