p(MGI:Slc40a1)
Expectedly, and in line with previous report (13), treatment of macrophages with DFO abolished ferroportin and ferritin induction by heme, whereas TfR1 expression was lowered upon heme and combined treatment with heme and DFO (Fig. 7D). PubMed:29212341
These data suggested that during severe hemolysis, heme mediated ferroportin induction and low hepcidin in HbS mice (11) served to elevate systemic iron availability, required to sustain high erythropoietic demands in these mice. PubMed:29212341
We showed that NAC treatment scavenged ROS production and, more importantly, it counteracted ferroportin induction by heme (Fig. 8B, C). PubMed:29212341
Heme induced the expression of Ho1 and Blvrb as well as Slc40a1, which encodes the mammalian iron exporter (Figure 5A), in agreement with previous reports (Delaby et al., 2008). PubMed:24630724
High ferroportin levels were measured in macrophages upon heme overload and erythrophagocytosis (12, 13, 31, 32, 37) and in hemolytic murine models of b-thalassemia and phenylhydrazineinduced hemolytic anemia (11, 22, 34). PubMed:29212341
These data suggested that during severe hemolysis, heme mediated ferroportin induction and low hepcidin in HbS mice (11) served to elevate systemic iron availability, required to sustain high erythropoietic demands in these mice. PubMed:29212341
Our in vivo observations could be recapitulated in isolated macrophages, which upon stimulation with heme (25 lM; 16 h) demonstrated increased ferroportin mRNA and protein expression (Fig. 4A, B) and a significant decrease in the intracellular iron pool (2.2-fold; p < 0.01) (Fig. 4C). PubMed:29212341
So far, our results established that in the conditions of acute and chronic heme overload, macrophages acquired high ferroportin expression and an efficient iron export. PubMed:29212341
Under heme overload conditions, macrophages acquire an iron phenotype characterized by low intracellular iron and high ferroportin expression. PubMed:29212341
We showed that simulation of macrophages with LPS resulted in significant reduction in ferroportin mRNA and protein expression and enhanced intracellular iron deposition throughout all time points tested (Fig. 5A–D). PubMed:29212341
This dramatically contrasts the iron phenotype that develops in response to LPS, hallmarked by high intracellular iron levels and low ferroportin expression (10, 20, 48). PubMed:29212341
By contrast, treatment of macrophages with PPIX failed to increase the ROS production and ferroportin expression, implying that iron within the heme moiety was required for the observed effects (Fig. 7B). PubMed:29212341
High ferroportin levels were measured in macrophages upon heme overload and erythrophagocytosis (12, 13, 31, 32, 37) and in hemolytic murine models of b-thalassemia and phenylhydrazineinduced hemolytic anemia (11, 22, 34). PubMed:29212341
Our study provides evidence that the increase in cellular oxidant levels, as a result of NADPH oxidase activity, was responsible for ferroportin induction by heme. PubMed:29212341
We show that heme, in a concentration range found during hemolytic episodes, increases intracellular ROS production and consequentially signals for ferroportin induction and subsequent iron export from the macrophages. PubMed:29212341
We showed that increase in ferroportin mRNA and protein expression by heme was effectively prevented in mice receiving combined treatment of NAC and heme (Fig. 8D, E). PubMed:29212341
We showed that cotreatment of macrophages with heme and apocynin (Fig. 7E), as well as with heme and allopurinol (Fig. 7F), fully prevented ferroportin induction by heme. These data revealed that inhibiting superoxide at its production site is an effective way to counteract heme-mediated ferroportin induction. PubMed:29212341
We showed that cotreatment of macrophages with heme and apocynin (Fig. 7E), as well as with heme and allopurinol (Fig. 7F), fully prevented ferroportin induction by heme. These data revealed that inhibiting superoxide at its production site is an effective way to counteract heme-mediated ferroportin induction. PubMed:29212341
Moreover, in CMs the heme-mediated induction of the iron exporter Ferroportin (Fpn) was abrogated by Hx treatment while the down-regulation of the iron importer Transferrin receptor 1 (TfR1) was significantly reduced by Hx (see Figure 3 in [37]) further indicating that Hx limits heme-iron accumulation within the cell. PubMed:28400318
In addition, ferroportin undergoes post-translational control by the systemic iron regulator, hepcidin, whereby binding of hepcidin to ferroportin causes its internalization and degradation, leading to iron retention within the cells (21, 41). PubMed:29212341
In addition, we observed an increase of ferroportin protein expression in duodenal enterocytes (Figure 3E and F). PubMed:28143953
In addition, despite an increase in ferritin expression, ferroportin expression was also induced in the liver of CEP mice (Figure 4E), suggesting an increase of iron release in the circulation to satisfy the high iron demand. PubMed:28143953
In addition, we observed an increase of ferroportin protein expression in duodenal enterocytes (Figure 3E and F). PubMed:28143953
In addition, despite an increase in ferritin expression, ferroportin expression was also induced in the liver of CEP mice (Figure 4E), suggesting an increase of iron release in the circulation to satisfy the high iron demand. PubMed:28143953
High ferroportin levels were measured in macrophages upon heme overload and erythrophagocytosis (12, 13, 31, 32, 37) and in hemolytic murine models of b-thalassemia and phenylhydrazineinduced hemolytic anemia (11, 22, 34). PubMed:29212341
These data suggested that during severe hemolysis, heme mediated ferroportin induction and low hepcidin in HbS mice (11) served to elevate systemic iron availability, required to sustain high erythropoietic demands in these mice. PubMed:29212341
Our in vivo observations could be recapitulated in isolated macrophages, which upon stimulation with heme (25 lM; 16 h) demonstrated increased ferroportin mRNA and protein expression (Fig. 4A, B) and a significant decrease in the intracellular iron pool (2.2-fold; p < 0.01) (Fig. 4C). PubMed:29212341
So far, our results established that in the conditions of acute and chronic heme overload, macrophages acquired high ferroportin expression and an efficient iron export. PubMed:29212341
Under heme overload conditions, macrophages acquire an iron phenotype characterized by low intracellular iron and high ferroportin expression. PubMed:29212341
High ferroportin levels were measured in macrophages upon heme overload and erythrophagocytosis (12, 13, 31, 32, 37) and in hemolytic murine models of b-thalassemia and phenylhydrazineinduced hemolytic anemia (11, 22, 34). PubMed:29212341
These data suggested that during severe hemolysis, heme mediated ferroportin induction and low hepcidin in HbS mice (11) served to elevate systemic iron availability, required to sustain high erythropoietic demands in these mice. PubMed:29212341
We showed that simulation of macrophages with LPS resulted in significant reduction in ferroportin mRNA and protein expression and enhanced intracellular iron deposition throughout all time points tested (Fig. 5A–D). PubMed:29212341
This dramatically contrasts the iron phenotype that develops in response to LPS, hallmarked by high intracellular iron levels and low ferroportin expression (10, 20, 48). PubMed:29212341
Our study provides evidence that the increase in cellular oxidant levels, as a result of NADPH oxidase activity, was responsible for ferroportin induction by heme. PubMed:29212341
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.