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; P<0.05). Metallothionein expression increased in cells treated with hepcidin as compared to control cells(P<0.05). ZIP14 expression remained unchanged (P>0.05), 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.Support or Funding InformationThe views expressed in this abstract are those of the authors and do not reflect the official policy of the Department of Army, Department of Defense, or the U.S. Government. Support provided by USAMRMC.