Role of the kidney in iron homeostasis: renal expression of Prohepcidin, Ferroportin, and DMT1 in anemic mice

Veuthey, Tania; D'Anna, María Cecilia; Roque, Marta Elena

doi:10.1152/ajprenal.90216.2008

Cited by 48 publications

(64 citation statements)

References 33 publications

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“…This result is consistent with that obtained by Wallace et al (2006), who reported prohepcidin localization in organelles, particularly Golgi apparatus, suggestive of proteins being accumulated in the secretory pathway prior to receiving a signal for secretion (Veuthey et al, 2008). In fact, under our experimental conditions, turpentine treatment lead to an increase in prohepcidin expression levels.…”

Section: Discussionsupporting

confidence: 93%

Immunohistochemical Studies on Duodenum, Spleen and Liver in Mice: Distribution of Ferroportin and Prohepcidin in an Inflammation Model

́Anna¹,

Giorgi

Roque

2011

Int. J. Morphol.

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D´ANNA, M. C.; GIORGI, G. & ROQUE, M. E.Immunohistochemical studies on duodenum, spleen and liver in mice: distribution of ferroportin and prohepcidin in an inflammation model. Int. J. Morphol., 29(3):747-753, 2011. SUMMARY:Duodenum, spleen and liver have a crucial role in iron balance on the whole organism and are the major sites of Ferroportin (FPN) expression. Specific regulations between FPN and hepcidin are responsible for changes seen in physiopathological conditions such as inflammation. We studied in vivo effects of turpentine oil-induced acute inflammation on FPN expression, and its relation with prohepcidin and iron mobilization. Immunohistochemical procedures were performed using rabbit anti-mouse FPN and prohepcidin antibodies with goat-labeled polymer-HRP anti-rabbit (DAB) as secondary antibody. Plasma and tissular iron were also studied. Our results showed a notable expression and redistribution of duodenal FPN to basolateral membrane in turpentine-treated mice, compared with supranuclear and the weak basolateral expression observed in healthy mice. Red pulp macrophages of healthy mice showed FPN-hemosiderin co-localization, compared with turpentine-treated mice which showed lack of FPN. In liver of healthy mice, FPN was seen in Kupffer cells, whereas in turpentine-treated mice decreased. In addition, we observed an increment of hepatic prohepcidin with a significant hypoferremia. Our findings demonstrated that acute inflammation induced a differential distribution of FPN, showing a cell type specific response. In macrophages, increased hepatic prohepcidin induced degradation of FPN, resulting in hypoferremia. In enterocytes, the redistribution observed of duodenal FPN reflects a different regulation in this tissue. The observed response of the proteins studied may be part of a cyclical pattern of systemic effects of acute inflammation on mouse tissue.

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Section: Discussionsupporting

confidence: 93%

Immunohistochemical Studies on Duodenum, Spleen and Liver in Mice: Distribution of Ferroportin and Prohepcidin in an Inflammation Model

́Anna¹,

Giorgi

Roque

2011

Int. J. Morphol.

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“…Emerging data, however, suggest that the kidney may be more extensively involved in iron metabolism than initially proposed. For instance, studies have revealed that multiple proteins involved in iron metabolism are expressed in the kidney, including hepcidin, FPN, and DMT-1 (43)(44)(45)(46)(47). Intriguingly, we found that deletion of FtH did not affect the expression of DMT-1 (expressed in late endosome/lysosome membranes of tubular cells), but was accompanied with diminution of FPN expression, in FtH PT-/-kidneys.…”

Section: Discussionmentioning

confidence: 41%

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

Zarjou¹,

Bolisetty²,

Joseph³

et al. 2013

J. Clin. Invest.

178

166

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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.

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“…There was no accumulation of iron in kidney suggesting that the kidney might be an effi cient way of eliminating excess iron. A recent study demonstrated that the kidney has the ability to express transferrin receptor-1 (TfR1), divalent metal transporter-1 (DMT 1), ferroportin-1 (FPN 1), iron regulatory protein (IRP), hepcidin (Hepc) and other iron metabolism proteins (Veuthey et al, 2008). However, our study also showed that lycopene treatment diminished the electron-dense ferritin storage and protected the mitochondrial membranes.…”

Section: Ultrastructural Alterations and Autophagy In Livermentioning

confidence: 42%

Protective effects of lycopene on oxidative stress, proliferation and autophagy in iron supplementation rats

et al. 2013

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Lycopene is common in diet and known for its antioxidant activities. However, the impact of lycopene on iron metabolism is poorly investigated. In this study, we hypothesize that lycopene can prevent iron-mediated oxidative stress, proliferation and autophagy in liver and use a rat model of nutritional iron supplementation to confi rm its intervention in these defence mechanisms. We found that iron supplementation induced cell proliferation predominantly in non parenchymal cells compared with hepatocytes, but not apoptosis. In addition, iron was accumulated within the hepatic lysosomes where it triggered autophagy as evidenced by the formation of autophagic vesicles detected by LC3-B staining. Iron supplementation also induced morphologic alterations of the mitochondrial membranes probably due to increased lipid peroxidation as indicated by elevated iron and malondialdehyde concentrations in serum and tissues. Lycopene reduced iron-catalyzed lipid peroxidation by decreasing the malondialdehyde level in the liver and colon and enhancing the total superoxide dismutase activities in serum and tissues. The result suggest that lycopene prevents iron-induced oxidative stress, proliferation and autophagy at both biochemical and histological levels due to its potent free radical scavenging and antioxidant properties.

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Role of the kidney in iron homeostasis: renal expression of Prohepcidin, Ferroportin, and DMT1 in anemic mice

Cited by 48 publications

References 33 publications

Immunohistochemical Studies on Duodenum, Spleen and Liver in Mice: Distribution of Ferroportin and Prohepcidin in an Inflammation Model

Immunohistochemical Studies on Duodenum, Spleen and Liver in Mice: Distribution of Ferroportin and Prohepcidin in an Inflammation Model

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

Protective effects of lycopene on oxidative stress, proliferation and autophagy in iron supplementation rats

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