Publication: Effect of iron overload on furin expression in wild-type and β-thalassemic mice
Issued Date
2015-01-10
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ISSN
22147500
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2-s2.0-84925507151
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Mahidol University
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SCOPUS
Bibliographic Citation
Toxicology Reports. Vol.2, (2015), 415-422
Suggested Citation
Surasak Wichaiyo, Paranee Yatmark, Ronald Enrique Morales Vargas, Pimtip Sanvarinda, Saovaros Svasti, Suthat Fucharoen, Noppawan Phumala Morales Effect of iron overload on furin expression in wild-type and β-thalassemic mice. Toxicology Reports. Vol.2, (2015), 415-422. doi:10.1016/j.toxrep.2015.01.004 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/36001
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Title
Effect of iron overload on furin expression in wild-type and β-thalassemic mice
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Abstract
© 2015 The Authors. 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.