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

Zarjou, Abolfazl and Bolisetty, Subhashini and Joseph, Reny and Traylor, Amie and Apostolov, Eugene and Arosio, Paolo and Balla, József and Verlander, Jill and Darshan, Deepak and Kuhn, Lucas C. and Agarwal, Anupam (2013) Proximal tubule H-ferritin mediates iron trafficking in acute kidney injury. JOURNAL OF CLINICAL INVESTIGATION, 123 (10). pp. 4423-4434. ISSN 0021-9738

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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.

Item Type: Article
Subjects: R Medicine / orvostudomány > RZ Other systems of medicine / orvostudomány egyéb területei
Depositing User: Dr. József Balla
Date Deposited: 14 Sep 2017 06:35
Last Modified: 14 Sep 2017 06:35
URI: http://real.mtak.hu/id/eprint/62381

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