title: Hephaestin and ceruloplasmin facilitate iron metabolism in the mouse kidney.
abstract: Multicopper ferroxidases (MCFs) play an important role in cellular iron homeostasis. However, the role of MCFs in renal metabolism remains unclear. We used Hephaestin (Heph) and Ceruloplasmin (Cp) single or double (Heph/Cp) knockout (KO) mice to study the roles of MCFs in the kidney. Renal iron levels and the expression of iron metabolism genes were examined. The non-heme iron content both in the renal cortex and medulla of Heph/Cp KO mice was significantly increased. Perls' Prussian blue staining showed iron accumulation on the apical side of renal tubular cells in Heph/Cp KO mice. A significant increase in ferritin protein expression was also observed in the renal medulla and cortex of Heph/Cp KO mice. Both DMT1 and TfR1 protein expression were significantly decreased in the renal medulla of Heph/Cp KO mice, while the expression of DMT1 protein was significantly increased in the renal cortex of these animals. Significant increase in proteinuria and total urinary iron was observed in the double knockout mice, and this was associated with compromised structural integrity. These results suggest that KO of both the HEPH and CP genes leads to kidney iron deposition and toxicity, MCFs could protect kidney against a damage from iron excess.
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, China.
authors.forename: Guohao
authors.initials: G
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, China.
authors.forename: Jiashuo
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, China.
authors.forename: Mengxia
authors.initials: M
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, China.
authors.forename: Zaitunamu
authors.initials: Z
authors.lastname: Maimaitiming
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, China.
authors.forename: Shunli
authors.initials: S
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, China.
authors.forename: Ruiwei
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Center for Environmental and Human Toxicology, Department of Physiological Sciences, University of Florida, Gainesville, FL, USA.
authors.forename: Brie K
authors.initials: BK
authors.lastname: Fuqua
authors.affiliation: FM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, PA, USA.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Dunaief
authors.affiliation: Center for Environmental and Human Toxicology, Department of Physiological Sciences, University of Florida, Gainesville, FL, USA.
authors.forename: Chris D
authors.initials: CD
authors.lastname: Vulpe
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Anderson
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, China.
authors.forename: Huijun
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D002570:Ceruloplasmin / Q000235:genetics* / Q000378:metabolism*; D003300:Copper / Q000737:chemistry; D005293:Ferritins / Q000378:metabolism; D005295:Ferrocyanides; D005838:Genotype; D006706:Homeostasis; D007501:Iron / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007672:Kidney Cortex; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D005295:Ferrocyanides; C117324:Heph protein, mouse; D008565:Membrane Proteins; D003300:Copper; D005293:Ferritins; D007501:Iron; D002570:Ceruloplasmin; C000170:ferric ferrocyanide