More recently, we have also shown that free heme is also released during storage and may mediate further inflammation28
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.
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.
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.
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.
Figures 5C-5D show that d7 propagation rates for nitrite oxidation correlate with both d7 and d35 cell-free oxyhemoglobin.
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).
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).
In other words, the faster rate of d7 nitrite oxidation predicted greater extents of oxidative damage incurred by the RBCs during storage.
Figure 2G shows storage also resulted in a significant increase in Prx-2 oxidation.
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.
Storage is known to result in increased hemolysis which in turn results in loss of NO-signaling, oxidative stress and inflammation post-transfusion.
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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.