Proximal tubule H-ferritin mediates iron trafficking in acute kidney injury
| Autor: | Abolfazl Zarjou, József Balla, Deepak Darshan, Eugene O. Apostolov, Anupam Agarwal, Jill W. Verlander, Reny Joseph, Lukas C. Kühn, Paolo Arosio, Amie M. Traylor, Subhashini Bolisetty |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Genotyping Techniques Iron Ferroportin 030232 urology & nephrology Lipocalin urologic and male genital diseases Ferroxidase activity Rhabdomyolysis ferritin iron trafficking Kidney Tubules Proximal Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Animals Cation Transport Proteins Heme DNA Primers 030304 developmental biology Mice Knockout chemistry.chemical_classification 0303 health sciences Base Sequence biology Acute kidney injury Biological Transport Hemopexin General Medicine Acute Kidney Injury medicine.disease Mice Inbred C57BL Ferritin Endocrinology Gene Expression Regulation chemistry Biochemistry Transferrin Apoferritins biology.protein |
| Zdroj: | Journal of Clinical Investigation. 123:4423-4434 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci67867 |
| Popis: | 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 (FtH(PT-/-) mice). FtH(PT-/-) 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 FtH(PT-/-) 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 FtH(PT-/-) 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. |
| Databáze: | OpenAIRE |
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