p(MGI:Hp)
Hepatic 4-hydroxynonenol (4-HNE), a marker of oxidative stress, was significantly lower in the liver microsomes of SSmice 24 hours after infusion of Hp or Hpx compared to vehicle-treated SS-mice (Fig 2G). PubMed:29694434
The beneficial effects of Hp and Hpx were lost by inhibition of HO with SnPP, but could be restored by CO administration. PubMed:29694434
The increase in plasma haptoglobin levels from baseline to 48 hours after resuscitation was less in mice transfused with SRBCs compared to mice transfused with FRBCs (P<0.001). PubMed:27515135
The beneficial effects of Hp and Hpx were lost by inhibition of HO with SnPP, but could be restored by CO administration. PubMed:29694434
Resuscitation with SRBCs together with albumin did not alter plasma levels of hemoglobin, hemopexin, haptoglobin, or heme as compared to resuscitation with SRBCs alone (Figure 3C–E, I, Supplemental Material and Supplemental Figure II A–B). PubMed:27515135
Pro-inflammatory cytokine RANTES (chemokine ligand 5 or CCL5), which recruits leukocytes to pro-inflammatory sites, was lower in the plasma of SS-mice 24 hours after infusion of Hp or Hpx compared to vehicle-treated SS-mice (Fig 2F). PubMed:29694434
Immunofluorescence staining of VCAM-1 and ICAM-1 was decreased in the dorsal skin of SS-mice 4h after infusion of Hb+Hp and Hb+Hpx compared to SS-mice infused with vehicle or Hb (Fig 2B and 2C). PubMed:29694434
Compared to Hb alone or Hb + albumin infused animals, sickle mice co-infused with Hb + Hp, Hb + Hpx, or Hb + Hp + Hpx had markedly diminished hepatic NF-κB activation 4h after infusion as evidenced by nuclear NF- κB phospho-p65 levels (Fig 2A). PubMed:29694434
Immunofluorescence staining of VCAM-1 and ICAM-1 was decreased in the dorsal skin of SS-mice 4h after infusion of Hb+Hp and Hb+Hpx compared to SS-mice infused with vehicle or Hb (Fig 2B and 2C). PubMed:29694434
Thus a single infusion of Hp or Hpx inhibited stasis for 48h. PubMed:29694434
Sickle mice co-infused with Hb + Hp, Hb + Hpx or Hb + Hp + Hpx had less stasis 1h after infusion than mice infused with Hb + albumin or Hb (Fig 1B). PubMed:29694434
Hp and Hpx significantly inhibited stasis in response H/R or LPS (Fig 5). PubMed:29694434
Congenital erythropoietic porphyria mice showed increased serum bilirubin and LDH levels (Table 1), with almost undetectable levels of Hp and Hpx (Figure 1A and B, respectively), which was strongly indicative of hemolytic anemia. PubMed:28143953
The Hp plasma concentration was very low in CEP mice (Figure 1A), probably because of an increased rate of its endocytosis and subsequent lysosomal degradation. PubMed:28143953
These findings are consistent with a recent study which showed that both Hp and hemopexin (heme scavenger) were equally effective in preventing vasoocclusion in a sickle cell mouse model infused with Hb [73]. PubMed:24486321
Likewise, 395 infusion of haptoglobin or hemopexin in HbS mice inhibited hemoglobin-dependent 396 vaso-occlusion (3). PubMed:28314763
Thus a single infusion of Hp or Hpx inhibited stasis for 48h. PubMed:29694434
Sickle mice co-infused with Hb + Hp, Hb + Hpx or Hb + Hp + Hpx had less stasis 1h after infusion than mice infused with Hb + albumin or Hb (Fig 1B). PubMed:29694434
Hp and Hpx significantly inhibited stasis in response H/R or LPS (Fig 5). PubMed:29694434
Hp attenuated HbFe21- and HbFe31-induced up-regulation of HO-1 and H-ferritin proteins (Figure 2B). PubMed:26974230
Interestingly, Hp attenuated the HbFe21- and HbFe31-induced HO-1 expression in the mitochondria (Figures 3A and 3B). PubMed:26974230
Hp attenuated HbFe21- and HbFe31-induced up-regulation of HO-1 and H-ferritin proteins (Figure 2B). PubMed:26974230
The increase in plasma haptoglobin levels from baseline to 48 hours after resuscitation was less in mice transfused with SRBCs compared to mice transfused with FRBCs (P<0.001). PubMed:27515135
Congenital erythropoietic porphyria mice showed increased serum bilirubin and LDH levels (Table 1), with almost undetectable levels of Hp and Hpx (Figure 1A and B, respectively), which was strongly indicative of hemolytic anemia. PubMed:28143953
The Hp plasma concentration was very low in CEP mice (Figure 1A), probably because of an increased rate of its endocytosis and subsequent lysosomal degradation. PubMed:28143953
By binding cell-free hemoglobin, haptoglobin prevents glomerular filtration of cell-free hemoglobin and subsequent kidney injury (2,7). PubMed:28314763
Schaer and colleagues 107 showed that administration of exogenous haptoglobin prevents extravasation of cell free hemoglobin and vasoconstriction in rats (18). PubMed:28314763
Furthermore, haptoglobin retained cell-free 338 hemoglobin in plasma and prevented hemoglobinuria. PubMed:28314763
In mice fed a HFD or in 339 diabetic mice fed a normal diet, haptoglobin mixed with murine tetrameric 340 hemoglobin in a 1:1 weight ratio also retained cell-free hemoglobin in plasma and 341 prevented hemoglobinuria but did not reduce hemoglobin-induced hypertension. PubMed:28314763
In the 358 current study, we demonstrated that administration of human haptoglobin retained 359 cell-free hemoglobin in plasma, prevented hemoglobinuria, and reduced the 360 hemoglobin-induced hypertension in healthy awake mice (see Figure 1A). PubMed:28314763
Recent data suggest that haptoglobin prevents hemoglobin-induced hypertension by 355 a similar mechanism (18). PubMed:28314763
In the 358 current study, we demonstrated that administration of human haptoglobin retained 359 cell-free hemoglobin in plasma, prevented hemoglobinuria, and reduced the 360 hemoglobin-induced hypertension in healthy awake mice (see Figure 1A). PubMed:28314763
Compared to Hb alone or Hb + albumin infused animals, sickle mice co-infused with Hb + Hp, Hb + Hpx, or Hb + Hp + Hpx had markedly diminished hepatic NF-κB activation 4h after infusion as evidenced by nuclear NF- κB phospho-p65 levels (Fig 2A). PubMed:29694434
Immunofluorescence staining of VCAM-1 and ICAM-1 was decreased in the dorsal skin of SS-mice 4h after infusion of Hb+Hp and Hb+Hpx compared to SS-mice infused with vehicle or Hb (Fig 2B and 2C). PubMed:29694434
Immunofluorescence staining of VCAM-1 and ICAM-1 was decreased in the dorsal skin of SS-mice 4h after infusion of Hb+Hp and Hb+Hpx compared to SS-mice infused with vehicle or Hb (Fig 2B and 2C). PubMed:29694434
Pro-inflammatory cytokine RANTES (chemokine ligand 5 or CCL5), which recruits leukocytes to pro-inflammatory sites, was lower in the plasma of SS-mice 24 hours after infusion of Hp or Hpx compared to vehicle-treated SS-mice (Fig 2F). PubMed:29694434
Hepatic 4-hydroxynonenol (4-HNE), a marker of oxidative stress, was significantly lower in the liver microsomes of SSmice 24 hours after infusion of Hp or Hpx compared to vehicle-treated SS-mice (Fig 2G). PubMed:29694434
The beneficial effects of Hp and Hpx were lost by inhibition of HO with SnPP, but could be restored by CO administration. PubMed:29694434
The beneficial effects of Hp and Hpx were lost by inhibition of HO with SnPP, but could be restored by CO administration. PubMed:29694434
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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.