Simple jQuery Dropdowns
Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/1839
Title: Effect of iron overload on furin expression in wild-type and β-thalassemic mice
Authors: Surasak Wichaiyo
Paranee Yatmark
Ronald Enrique Morales Vargas
Pimtip Sanvarinda
Saovaros Svasti
Suthat Fucharoen
Noppawan Phumala Morales
Mahidol University. Institute of Molecular Biosciences. Thalassemia Research Center
Mahidol University. Faculty of Tropical Medicine. Department of Medical Entomology
Keywords: Furin;Hepcidin;Iron overload;β-Thalassemic mice;Open Access article
Issue Date: 2015
Citation: Toxicology Reports. Vol.2, 2015, 415-422
Abstract: Furin is a proprotein convertase enzyme. In the liver, it cleaves prohepcidin to form active hepcidin-25, which regulates systemic iron homeostasis. Hepcidin deficiency is a component of several iron overload disorders, including β-thalassemia. Several studies have identified factors that repress hepcidin gene transcription in iron overload. However, the effect of iron overload on furin, a post-translational regulator of hepcidin, has never been evaluated. The present study aimed to investigate the changes in furin and related factors in parenteral iron-overloaded mice, including those with β-thalassemia. Wild-type (WT) and β-thalassemia intermedia (th3/+) C57BL/6 mice were intraperitoneally injected with 9 doses of iron dextran (1 g iron/kg body weight) over 2 weeks. In the iron overload condition, our data demonstrated a significant Furin mRNA reduction in WT and th3/+ mice. In addition, the liver furin protein level in iron-overloaded WT mice was significantly reduced by 70% compared to control WT mice. However, the liver furin protein in iron-overloaded th3/+ mice did not show a significant reduction compared to control th3/+ mice. The hepcidin gene (hepcidin antimicrobial peptide gene, Hamp1) expression was increased in iron-overloaded WT and th3/+ mice. Surprisingly, the liver hepcidin protein level and total serum hepcidin were not increased in both WT and th3/+ mice with iron overload, regardless of the increase in Hamp1 mRNA. In conclusion, we demonstrate furin downregulation in conjunction with Hamp1 mRNA-unrelated pattern of hepcidin protein expression in iron-overloaded mice, particularly the WT mice, suggesting that, not only the amount of hepcidin but also the furin-mediated physiological activity may be decreased in severe iron overload condition.
URI: http://repository.li.mahidol.ac.th/dspace/handle/123456789/1839
metadata.dc.identifier.url: http://www.sciencedirect.com/science/article/pii/S2214750015000062
Appears in Collections:MB-Article

Files in This Item:
File Description SizeFormat 
mb-ar-saovasos-2015.pdf1.27 MBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.