Kinetic and stoichiometric constraints determine the pathway of H 2 O 2 consumption by red blood cells

Orrico, Florencia; Möller, Matías N.; Cassina, Adriana; Denicolab, Ana; Thomsona, Leonor

doi:10.1016/j.freeradbiomed.2018.04.118

Cited by 2 publications

(3 citation statements)

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“…[2][3][4] Modeling studies suggest that Prx-2 activity is reversibly inhibited in RBCs under basal conditions, and other studies have demonstrated that experimental conditions related to cell density and timing are variables in Prx-2 activity. 24,25 Emerging data also show that peroxidatic activity of Prx-2 is altered by oxidative modifications (e.g., nitration 26 ). Collectively these insights suggest that despite Prx-2 protein levels being relatively high in a cell devoid of protein synthesis, Prx-2 activity in RBCs may be limiting under certain conditions.…”

Section: Discussionmentioning

confidence: 98%

Peroxiredoxin‐2 recycling is slower in denser and pediatric sickle cell red cells

Bae

Kasztan

et al. 2022

The FASEB Journal

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Peroxiredoxin‐2 (Prx‐2) is a critical antioxidant protein in red blood cells (RBC). Prx‐2 is oxidized to a disulfide covalently‐bound dimer by H2O2, and then reduced back by the NADPH‐dependent thioredoxin—thioredoxin reductase system. The reduction of oxidized Prx‐2 is relatively slow in RBCs. Since Prx‐2 is highly abundant, Prx‐2s' peroxidase catalytic cycle is not considered to be limiting under normal conditions. However, whether Prx‐2 recycling becomes limiting when RBCs are exposed to stress is not known. Using three different model systems characterized by increased oxidative damage to RBCs spanning the physiologic (endogenous RBCs of different ages), therapeutic (cold‐stored RBCs in blood banks) and pathologic (RBCs from sickle cell disease (SCD) patients and humanized SCD mice) spectrum, basal levels of Prx‐2 oxidation and Prx‐2 recycling kinetics after addition of H2O2 were determined. The reduction of oxidized Prx‐2 was significantly slower in older versuin older versus younger RBCs, in RBCs stored for 4–5 weeks compared to 1 week, and in RBC from pediatric SCD patients compared to RBCs from control non‐SCD patients. Similarly, the rate of Prx‐2 recycling was slower in humanized SCD mice compared to WT mice. Treatment of RBC with carbon monoxide (CO) to limit heme‐peroxidase activity had no effect on Prx‐2 recycling kinetics. Treatment with glucose attenuated slowed Prx‐2 recycling in older RBCs and SCD RBCs, but not stored RBCs. In conclusion, the reduction of oxidized Prx‐2 can be further slowed in RBCs, which may limit the protection afforded by this antioxidant protein in settings associated with erythrocyte stress.

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Section: Discussionmentioning

confidence: 98%

Peroxiredoxin‐2 recycling is slower in denser and pediatric sickle cell red cells

Bae

Kasztan

et al. 2022

The FASEB Journal

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“…In the cell, hydrogen peroxide is reduced to water with the participation of enzymes Cat and Gpx [7]. At high concentrations of hydrogen peroxide, Cat is the main participant in the H 2 O 2 utilization, as the rate constant of this reaction is higher than that of other enzymes and at the same time it does not require additional substrates.…”

Section: Description Of the Modelmentioning

confidence: 99%

“…The effect of such signals is reversible, as evidenced by the presence in the cell of a special set of enzymatic systems, including catalase (CAT), glutathione peroxidase (GPX), peroxyredoxin (PRX), etc. [2,[5][6][7]. A moderate increase in the concentration of hydrogen peroxide activates mechanisms associated with protection and adaptation [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Regulation of the Structural Stability of Erythrocytes by Hydrogen Peroxide: Mathematical Model and Experiment

Voinarouski

Мартинович

2022

Biochem. Moscow Suppl. Ser. A

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In this study, the regulatory mechanisms induced by extracellular hydrogen peroxide were analyzed on the basis of a mathematical model that considers the key stages of the formation of methemoglobin and ferrylhemoglobin, as well as their binding to the erythrocyte membrane. Numerical modeling has shown that reversible binding of methemoglobin to the membrane is an adaptive mechanism aimed at stabilizing the lipid bilayer of the membrane. On the other hand, an increase in the concentration of ferrylhemoglobin and its binding to the membrane leads to an increase in pathophysiological processes that reduce the structural stability of cells. The quantity of methemoglobins and ferrylhemoglobins formed depends on the concentration of extracellular hydrogen peroxide and exposition time, the number of cells in the sample, the state of the antioxidant system of erythrocytes, the metabolic activity of cells and external metabolic conditions. Based on numerical modeling, optimal conditions (oxidant concentration and exposition time) have been determined, under which the activation of adaptive processes occurs. Experiments with erythrocyte hemolysis in vitro have shown that hydrogen peroxide at concentrations of 10-200 μM causes an increase in the structural stability of the membrane and a decrease in the proportion of hemolyzed erythrocytes.

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Kinetic and stoichiometric constraints determine the pathway of H 2 O 2 consumption by red blood cells

Cited by 2 publications

References 0 publications

Peroxiredoxin‐2 recycling is slower in denser and pediatric sickle cell red cells

Peroxiredoxin‐2 recycling is slower in denser and pediatric sickle cell red cells

Regulation of the Structural Stability of Erythrocytes by Hydrogen Peroxide: Mathematical Model and Experiment

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