p(HGNC:HPX)
This ATP depletion was prevented by the addition of the heme scavenger, hemopexin (Figure 5b). PubMed:26794659
Treatment with Hx or DFO diminished the increase of some M1 polarization markers in BMDMs following treatment with hemolytic RBCs (supplemental Figure 14). PubMed:26675351
Correlation analysis using Pearson’s correlation coefficient showed statistically significant inverse correlation between Hpx and blood pressure, both systolic (r = -0.511, pvalue< 0.00001, n = 145) and diastolic (r = -0,520, p-value<0.00001, n = 145)(Fig 3). PubMed:26368565
In addition, Hx and DFO prevented the heme- and ironmediated induction of the M1 markers MHCII, CD86, CD14, and TNFα and the decrease of some M2 markers, such as CD206, IL-10, and Arginase-1 (the last for FeNTA only) in M0 BMDMs (Figure 6A; supplemental Figure 15A). PubMed:26675351
In addition, Hx and DFO prevented the heme- and ironmediated induction of the M1 markers MHCII, CD86, CD14, and TNFα and the decrease of some M2 markers, such as CD206, IL-10, and Arginase-1 (the last for FeNTA only) in M0 BMDMs (Figure 6A; supplemental Figure 15A). PubMed:26675351
In addition, Hx and DFO prevented the heme- and ironmediated induction of the M1 markers MHCII, CD86, CD14, and TNFα and the decrease of some M2 markers, such as CD206, IL-10, and Arginase-1 (the last for FeNTA only) in M0 BMDMs (Figure 6A; supplemental Figure 15A). PubMed:26675351
Studies of sickle cell anemia patients have reported decreased levels of Hpx following hemolysis [68]. PubMed:26368565
Analysis of the intravascular heme-scavenger protein Hpx showed a statistically significant decrease in plasma Hpx concentration of women with PE (p-value<0.0001) as compared to the controls (Table 3). PubMed:26368565
In cases of extensive and chronic hemolysis, levels of haptoglobin and hemopexin in plasma decrease markedly [20,21]. PubMed:26875449
Plasma haptoglobin and hemopexin levels are often depleted in SCD patients and mice due to chronic intravascular hemolysis [21±24]. PubMed:29694434
Moreover, the heme-binding protein, hemopexin, also suppressed the oxidation of lipid by ferro- and ferrihemoglobin, indicating the necessity for heme release from ferrihemoglobin for this oxidative process. PubMed:20378845
Both the hemoglobin-binding protein, haptoglobin,27 and the heme-binding protein, hemopexin, inhibited such oxidative modification of lipids indicating the importance of heme loss and scission in hemoglobin-provoked oxidation of lipids derived from atheromatous lesions. PubMed:20378845
Inhibition of lipid oxidation by either haptoglobin or hemopexin reduced the cytotoxicity (Fig 4B) and HO-1 induction caused by sublethal amounts of pretreated atheromatous lesion lipids (Fig 4C and D). PubMed:20378845
The heme-binding protein, hemopexin, which likely prevents heme:lipid interactions and blocks the oxidative scission of heme,26 significantly inhibited the oxidative reactions. PubMed:20378845
We have found that atheroma lipids when oxidized by heme are highly cytotoxic to human endothelial cells, and hemopexin reduced this cytotoxicity. PubMed:20378845
Importantly, heme b interaction with heme oxygenase (HO; Lad et al., 2003), the enzyme responsible for heme intracellular catabolism, and hemopexin (Hx; Paoli et al., 1999), a plasmatic heme scavenger, is essential for the regulation of free heme availability and Fe recycling (Kovtunovych et al., 2010; Tolosano et al., 2010). PubMed:24904418
Based on clinical observations the Hb and heme scavenger proteins haptoglobin (Hp) and hemopexin (Hx) have been characterized as a sequential defense system with Hp as the primary protector and Hx as a backup when all Hp is depleted during more severe intravascular hemolysis. PubMed:26475040
Recently, we demonstrated that Hx controls hepatic heme uptake and thus limits heme accumulation in extrahepatic tissues, such as the vessel wall and the heart, preventing heme-induced toxicity and tissue injury. PubMed:26675351
Taken together, these data demonstrate that Hx limits macrophage heme overload and prevents the prooxidant and proinflammatory effects triggered by heme in cellular assays and in vivo. PubMed:26675351
Thus, the interactions of hemoglobin with haptoglobin, and of heme with hemopexin, ensure safe disposal of potentially dangerous molecules [6,7,15–19] PubMed:26875449
Heme released from cell-free hemoglobin on oxidation is bound by hemopexin and degraded by hepatocytes in the liver [12]. PubMed:29956069
Of the biological components known to bind hemin, Hpx is by far the most efficient with a dissociation constant (Kd) lower than 1 x 10–13 M; as a result, after binding, the transfer of hemin from Hpx to other proteins or lipids is not possible [24]. PubMed:30281034
On the extracellular level, within the circulation, haptoglobin (Hp) and hemopexin (Hpx) are two of the most prominent scavenger proteins, with antioxidative properties through their capacity to remove cell-free Hb (by Hp) and heme (by Hpx). PubMed:30505280
Hx inhibits the oxidative property of heme (Eskew et al., 1999) and mediates heme transportation to intracellular compartments through the macrophage receptor CD91 (Hvidberg et al., 2005), a critical step on heme catabolism. PubMed:24904418
In fact, hemolysis or heme injection in Hx−/− mice cause increased inflammation and severe renal damage compared to wild type (WT) mice (Tolosano et al., 1999; Vinchi et al., 2008). PubMed:24904418
In fact, hemolysis or heme injection in Hx−/− mice cause increased inflammation and severe renal damage compared to wild type (WT) mice (Tolosano et al., 1999; Vinchi et al., 2008). PubMed:24904418
Analysis of the intravascular heme-scavenger protein Hpx showed a statistically significant decrease in plasma Hpx concentration of women with PE (p-value<0.0001) as compared to the controls (Table 3). PubMed:26368565
Correlation analysis using Pearson’s correlation coefficient showed statistically significant inverse correlation between Hpx and blood pressure, both systolic (r = -0.511, pvalue< 0.00001, n = 145) and diastolic (r = -0,520, p-value<0.00001, n = 145)(Fig 3). PubMed:26368565
However, no changes in peroxidase activity were observed after incubation with haptoglobin or hemopexin (Fig. 2). PubMed:28088643
Studies of sickle cell anemia patients have reported decreased levels of Hpx following hemolysis [68]. PubMed:26368565
Taken together, these data demonstrate that Hx limits macrophage heme overload and prevents the prooxidant and proinflammatory effects triggered by heme in cellular assays and in vivo. PubMed:26675351
Taken together, these data demonstrate that Hx limits macrophage heme overload and prevents the prooxidant and proinflammatory effects triggered by heme in cellular assays and in vivo. PubMed:26675351
Treatment with Hx or DFO diminished the increase of some M1 polarization markers in BMDMs following treatment with hemolytic RBCs (supplemental Figure 14). PubMed:26675351
In addition, Hx and DFO prevented the heme- and ironmediated induction of the M1 markers MHCII, CD86, CD14, and TNFα and the decrease of some M2 markers, such as CD206, IL-10, and Arginase-1 (the last for FeNTA only) in M0 BMDMs (Figure 6A; supplemental Figure 15A). PubMed:26675351
In addition, Hx and DFO prevented the heme- and ironmediated induction of the M1 markers MHCII, CD86, CD14, and TNFα and the decrease of some M2 markers, such as CD206, IL-10, and Arginase-1 (the last for FeNTA only) in M0 BMDMs (Figure 6A; supplemental Figure 15A). PubMed:26675351
Plasma haptoglobin and hemopexin levels are often depleted in SCD patients and mice due to chronic intravascular hemolysis [21±24]. PubMed:29694434
In addition, Hx and DFO prevented the heme- and ironmediated induction of the M1 markers MHCII, CD86, CD14, and TNFα and the decrease of some M2 markers, such as CD206, IL-10, and Arginase-1 (the last for FeNTA only) in M0 BMDMs (Figure 6A; supplemental Figure 15A). PubMed:26675351
In addition, Hx and DFO prevented the heme- and ironmediated induction of the M1 markers MHCII, CD86, CD14, and TNFα and the decrease of some M2 markers, such as CD206, IL-10, and Arginase-1 (the last for FeNTA only) in M0 BMDMs (Figure 6A; supplemental Figure 15A). PubMed:26675351
In addition, Hx and DFO prevented the heme- and ironmediated induction of the M1 markers MHCII, CD86, CD14, and TNFα and the decrease of some M2 markers, such as CD206, IL-10, and Arginase-1 (the last for FeNTA only) in M0 BMDMs (Figure 6A; supplemental Figure 15A). PubMed:26675351
In addition, Hx and DFO prevented the heme- and ironmediated induction of the M1 markers MHCII, CD86, CD14, and TNFα and the decrease of some M2 markers, such as CD206, IL-10, and Arginase-1 (the last for FeNTA only) in M0 BMDMs (Figure 6A; supplemental Figure 15A). PubMed:26675351
In addition, Hx and DFO prevented the heme- and ironmediated induction of the M1 markers MHCII, CD86, CD14, and TNFα and the decrease of some M2 markers, such as CD206, IL-10, and Arginase-1 (the last for FeNTA only) in M0 BMDMs (Figure 6A; supplemental Figure 15A). PubMed:26675351
This ATP depletion was prevented by the addition of the heme scavenger, hemopexin (Figure 5b). PubMed:26794659
In cases of extensive and chronic hemolysis, levels of haptoglobin and hemopexin in plasma decrease markedly [20,21]. PubMed:26875449
Vinchi and co-workers proved that the hemoglobin scavenger hemopexin prevents from hepatic microvascular stasis induced by intravascular hemolysis (using a mouse model of heme overloadin wild-typemicecomparedtohemopexin-nullmice) [116]. PubMed:29956069
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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.