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PubMed: 26202471

Title
Predicting storage-dependent damage to red blood cells using nitrite oxidation kinetics, peroxiredoxin-2 oxidation, and hemoglobin and free heme measurements.
Journal
Transfusion
Volume
55
Issue
None
Pages
2967-78
Date
2015-12-01
Authors
Harper V | Marques MB | Oh JY | Patel RP | Stapley R

Evidence e73da9bcb7
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More recently, we have also shown that free heme is also released during storage and may mediate further inflammation28

a(CHEBI:heme) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

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a(CHEBI:heme) positiveCorrelation a(HM:"stored erythrocytes") View Subject | View Object

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a(HM:"stored erythrocytes") positiveCorrelation a(CHEBI:heme) View Subject | View Object

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path(MESH:Inflammation) positiveCorrelation a(CHEBI:heme) View Subject | View Object

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Evidence 0d233f8026
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Prx-2 has emerged as the key antioxidant protein that protects RBCs against biologically relevant concentrations of H2O2 produced endogenously (via hemoglobin autoxidation) or exogenously by inflammatory cells25,26.

a(CHEBI:"hydrogen peroxide") negativeCorrelation p(HGNC:PRDX2) View Subject | View Object

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p(HGNC:PRDX2) negativeCorrelation a(CHEBI:"hydrogen peroxide") View Subject | View Object

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Evidence 18cfbd3317
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Figures 2A-F show changes in oxyhemoglobin, methemoglobin and free heme in both the intraerythrocytic and supernatant fractions in both d7 and d35 RBC. Significant storage-dependent increases for all species in the cell-free fraction were observed, with no storage-dependent differences observed in the erythrocyte.

a(CHEBI:heme) positiveCorrelation a(HM:"stored erythrocytes") View Subject | View Object

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a(CHEBI:methemoglobin) positiveCorrelation a(HM:"stored erythrocytes") View Subject | View Object

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a(CHEBI:oxyhemoglobin) positiveCorrelation a(HM:"stored erythrocytes") View Subject | View Object

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a(HM:"stored erythrocytes") positiveCorrelation a(CHEBI:oxyhemoglobin) View Subject | View Object

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a(HM:"stored erythrocytes") positiveCorrelation a(CHEBI:methemoglobin) View Subject | View Object

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a(HM:"stored erythrocytes") positiveCorrelation a(CHEBI:heme) View Subject | View Object

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Evidence 403ee7b3c7
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Figures 5A-5B, show that at d7, faster rates for nitrite oxidation in the lag phase were positively associated with higher concentrations of extracellular free heme at d7 and d35.

a(CHEBI:heme) positiveCorrelation a(HM:"nitrite oxidation") View Subject | View Object

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a(HM:"nitrite oxidation") positiveCorrelation a(CHEBI:heme) View Subject | View Object

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Evidence 5b5980bd11
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We have also shown that older RBCs oxidize nitrite with faster rates compared to younger RBCs, which may account for decreased circulating nitrite levels in trauma patients receiving older RBCs14.

a(CHEBI:nitrite) negativeCorrelation a(HM:"stored erythrocytes") View Subject | View Object

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a(HM:"stored erythrocytes") negativeCorrelation a(CHEBI:nitrite) View Subject | View Object

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Evidence 594b342190
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Figures 5C-5D show that d7 propagation rates for nitrite oxidation correlate with both d7 and d35 cell-free oxyhemoglobin.

a(CHEBI:oxyhemoglobin) positiveCorrelation a(HM:"nitrite oxidation") View Subject | View Object

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a(HM:"nitrite oxidation") positiveCorrelation a(CHEBI:oxyhemoglobin) View Subject | View Object

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Evidence f34d2d863d
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Figures 4B-D shows that d7 Prx-2 oxidation correlates positively with nitrite oxidation kinetics in the lag phase (i.e. inversely with lag time, positively with lag rates, Figures 4B-C respectively).

a(HM:"nitrite oxidation") positiveCorrelation p(MGI:Prdx2) View Subject | View Object

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p(MGI:Prdx2) positiveCorrelation a(HM:"nitrite oxidation") View Subject | View Object

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Evidence ab0499f213
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Figure 5E shows that d7 nitrite oxidation propagation rates also positively correlate with the extent of Prx-2 oxidation that occurred during storage (i.e. d35 – d7 Prx-2 oxidation in RBC).

a(HM:"nitrite oxidation") positiveCorrelation p(MGI:Prdx2) View Subject | View Object

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p(MGI:Prdx2) positiveCorrelation a(HM:"nitrite oxidation") View Subject | View Object

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Evidence 8999984a33
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In other words, the faster rate of d7 nitrite oxidation predicted greater extents of oxidative damage incurred by the RBCs during storage.

a(HM:"nitrite oxidation") positiveCorrelation bp(MESH:"Oxidative Stress") View Subject | View Object

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bp(MESH:"Oxidative Stress") positiveCorrelation a(HM:"nitrite oxidation") View Subject | View Object

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Evidence a0dbc897a0
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Figure 2G shows storage also resulted in a significant increase in Prx-2 oxidation.

a(HM:"stored erythrocytes") positiveCorrelation p(MGI:Prdx2) View Subject | View Object

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p(MGI:Prdx2) positiveCorrelation a(HM:"stored erythrocytes") View Subject | View Object

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Evidence 0c2a460f81
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The higher the basal (d7) level of Prx-2 oxidation, the higher the level of Prx-2 oxidation in the same RBC after 35 days of storage.

a(HM:"stored erythrocytes") positiveCorrelation p(MGI:Prdx2) View Subject | View Object

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p(MGI:Prdx2) positiveCorrelation a(HM:"stored erythrocytes") View Subject | View Object

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Evidence 264d2b164a
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Storage is known to result in increased hemolysis which in turn results in loss of NO-signaling, oxidative stress and inflammation post-transfusion.

a(HM:"stored erythrocytes") positiveCorrelation path(MESH:Hemolysis) View Subject | View Object

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a(HM:"stored erythrocytes") positiveCorrelation bp(GO:"nitric oxide mediated signal transduction") View Subject | View Object

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a(HM:"stored erythrocytes") positiveCorrelation bp(MESH:"Oxidative Stress") View Subject | View Object

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a(HM:"stored erythrocytes") positiveCorrelation path(MESH:Inflammation) View Subject | View Object

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bp(GO:"nitric oxide mediated signal transduction") positiveCorrelation a(HM:"stored erythrocytes") View Subject | View Object

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bp(MESH:"Oxidative Stress") positiveCorrelation a(HM:"stored erythrocytes") View Subject | View Object

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path(MESH:Hemolysis) positiveCorrelation a(HM:"stored erythrocytes") View Subject | View Object

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path(MESH:Inflammation) positiveCorrelation a(HM:"stored erythrocytes") View Subject | View Object

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