Proximal tubule H-ferritin mediates iron trafficking in acute kidney injury

Zarjou, Abolfazl, Bolisetty, Subhashini, Joseph, Reny, Traylor, Amie, Apostolov, Eugene O., Arosio, Paolo, Balla, Jozsef, Verlander, Jill, Darshan, Deepak, Kuhn, Lukas C. and Agarwal, Anupam (2013) Proximal tubule H-ferritin mediates iron trafficking in acute kidney injury. Journal of Clinical Investigation, 123 10: 4423-4434. doi:10.1172/JCI67867


Author Zarjou, Abolfazl
Bolisetty, Subhashini
Joseph, Reny
Traylor, Amie
Apostolov, Eugene O.
Arosio, Paolo
Balla, Jozsef
Verlander, Jill
Darshan, Deepak
Kuhn, Lukas C.
Agarwal, Anupam
Title Proximal tubule H-ferritin mediates iron trafficking in acute kidney injury
Journal name Journal of Clinical Investigation   Check publisher's open access policy
ISSN 0021-9738
1558-8238
Publication date 2013-10
Year available 2013
Sub-type Article (original research)
DOI 10.1172/JCI67867
Open Access Status DOI
Volume 123
Issue 10
Start page 4423
End page 4434
Total pages 12
Place of publication Ann Arbor, MI, United States
Publisher American Society for Clinical Investigation
Collection year 2014
Language eng
Formatted abstract
Ferritin plays a central role in iron metabolism and is made of 24 subunits of 2 types: heavy chain and light chain. The ferritin heavy chain (FtH) has ferroxidase activity that is required for iron incorporation and limiting toxicity. The purpose of this study was to investigate the role of FtH in acute kidney injury (AKI) and renal iron handling by using proximal tubule–specific FtH-knockout mice (FtHPT–/– mice). FtHPT–/– mice had significant mortality, worse structural and functional renal injury, and increased levels of apoptosis in rhabdomyolysis and cisplatin-induced AKI, despite significantly higher expression of heme oxygenase-1, an antioxidant and cytoprotective enzyme. While expression of divalent metal transporter-1 was unaffected, expression of ferroportin (FPN) was significantly lower under both basal and rhabdomyolysis-induced AKI in FtHPT–/– mice. Apical localization of FPN was disrupted after AKI to a diffuse cytosolic and basolateral pattern. FtH, regardless of iron content and ferroxidase activity, induced FPN. Interestingly, urinary levels of the iron acceptor proteins neutrophil gelatinase–associated lipocalin, hemopexin, and transferrin were increased in FtHPT–/– mice after AKI. These results underscore the protective role of FtH and reveal the critical role of proximal tubule FtH in iron trafficking in AKI.
Keyword Acute renal failure
Ischemia/reperfusion injury
Cisplatin induced nephrotoxicity
Antimicrobial peptide hepcidin
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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