Impaired erythrocyte methemoglobin reduction in sickle cell disease: dependence of methemoglobin reduction on reduced nicotinamide adenine dinucleotide content

Zerez, CR; Lachant, NA; Tanaka, KR

doi:10.1182/blood.v76.5.1008.bloodjournal7651008

Cited by 5 publications

(7 citation statements)

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“…No differences in microparticle levels were observed between any RBC preparation, with levels (expressed as percent of total RBC) being 0.21 -0.07, 0.26 -0.09, and 0.43 -0.18 for UF, young, and old RBC, respectively (data are mean -SEM, n = 3. p = 0.62 by 1way repeated measures-analysis of variance [RM-ANOVA]). Finally, we note that previous studies have shown*2-fold lower methemoglobin reductase activities in older RBC compared with younger RBC (60). This could, in turn, affect NOdioxygenation kinetics by altering the concentration of oxyhemolobin in the RBC.…”

Section: Effects Of Rbc Age On No Reactions and Signalingmentioning

confidence: 64%

Effects of Erythrocyte Aging on Nitric Oxide and Nitrite Metabolism

Owusu

Stapley²,

Honavar³

et al. 2013

Antioxidants & Redox Signaling

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Section: Effects Of Rbc Age On No Reactions and Signalingmentioning

confidence: 64%

Effects of Erythrocyte Aging on Nitric Oxide and Nitrite Metabolism

Owusu

Stapley²,

Honavar³

et al. 2013

Antioxidants & Redox Signaling

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“…NADH production via reverse flux of LDH should result in an increase in pyruvate concentration in plasma. In fact, it has been reported that oxidative stress causes an accumulation of pyruvate in plasma [38], because of its release from erythrocytes [26]. As we described above, cells in which there is an active tricarboxylic acid cycle would be able to harness the reducing power of the cycle and be tolerant to oxidative stress.…”

Section: Discussionmentioning

confidence: 86%

Simulation study of methemoglobin reduction in erythrocytes

et al. 2007

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In an integrative approach to gaining a better understanding of cell-wide molecular networks at the systems level (systems biology), many attempts at computer simulations of metabolic networks have been made. Because of the simplicity of its structure and components, and the availability of kinetic information, erythrocyte metabolism has been the focus of mathematical modeling for over three decades [1], and is a leading example of the use of mathematical modeling not only for understanding biochemical regulation, but also as the basis for the construction of other mathematical frameworks [2][3][4][5]. For example, models of erythrocyte metabolism were able to predict the importance of the de novo synthesis of glutathione and its mechanism of action in glucose-6-phosphate dehydrogenase (G6PDH)-deficient cells [6], and to analyze Methemoglobin (metHb), an oxidized form of hemoglobin, is unable to bind and carry oxygen. Erythrocytes are continuously subjected to oxidative stress and nitrite exposure, which results in the spontaneous formation of metHb. To avoid the accumulation of metHb, reductive pathways mediated by cytochrome b5 or flavin, coupled with NADH-dependent or NADPH-dependent metHb reductases, respectively, keep the level of metHb in erythrocytes at less than 1% of the total hemoglobin under normal conditions. In this work, a mathematical model has been developed to quantitatively assess the relative contributions of the two major metHbreducing pathways, taking into consideration the supply of NADH and NADPH from central energy metabolism. The results of the simulation experiments suggest that these pathways have different roles in the reduction of metHb; one has a high response rate to hemoglobin oxidation with a limited reducing flux, and the other has a low response rate with a high capacity flux. On the basis of the results of our model, under normal oxidative conditions, the NADPH-dependent system, the physiological role of which to date has been unclear, is predicted to be responsible for most of the reduction of metHb. In contrast, the cytochrome b5-NADH pathway becomes dominant under conditions of excess metHb accumulation, only after the capacity of the flavin-NADPH pathway has reached its limit. We discuss the potential implications of a system designed with two metHbreducing pathways in human erythrocytes.Abbreviations cytb5, cytochrome b5; cytb5R, (NADH-dependent) cytochrome b5 reductase; FR, (NADPH-dependent) flavin reductase; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; G6PDH, glucose-6-phosphate dehydrogenase; GSSG, oxidized glutathione; GSH, glutathione (reduced form); LDH, lactate dehydrogenase; metHb, methemoglobin.

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“…Oxyhemoglobin desaturation (OHD) is a well‐documented phenomenon in patients with SCD 1–7. The OHD is attributed to hypoxemia and a low arterial partial pressure of oxygen (PaO 2 ), the rightward shift of the oxyhemoglobin dissociation curve, and elevated levels of dyshemoglobins 8–14. Carboxyhemoglobin (COHb) and methemoglobin (MetHb), elevated in the presence of intravascular hemolysis, are dysfunctional forms of hemoglobin incapable of transporting oxygen, resulting in decreased arterial oxygen content 10–14.…”

Section: Introductionmentioning

confidence: 99%

Non‐invasive measurements of carboxyhemoglobin and methemoglobin in children with sickle cell disease

Caboot

Jawad

McDonough

et al. 2012

Pediatric Pulmonology

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SUMMARY Assessment of oxyhemoglobin saturation in patients with sickle cell disease (SCD) is vital for prompt recognition of hypoxemia. The accuracy of pulse oximeter measurements of blood oxygenation in SCD patients is variable, partially due to carboxyhemoglobin (COHb) and methemoglobin (MetHb), which decrease the oxygen content of blood. This study evaluated the accuracy and reliability of a non-invasive pulse co-oximeter in measuring COHb and MetHb percentages (SpCO and SpMet) in children with SCD. We hypothesized that measurements of COHb and MetHb by non-invasive pulse co-oximetry agree within acceptable clinical accuracy with those made by invasive whole blood co-oximetry. Fifty children with SCD-SS underwent pulse co-oximetry and blood co-oximetry while breathing room air. Non-invasive COHb and MetHb readings were compared to the corresponding blood measurements. The pulse co-oximeter bias was 0.1% for COHb and −0.22% for MetHb. The precision of the measured SpCO was ±2.1% within a COHb range of 0.4–6.1%, and the precision of the measured SpMet was ±0.33% within a MetHb range of 0.1–1.1%. Non-invasive pulse co-oximetry was useful in measuring COHb and MetHb levels in children with SCD. Although the non-invasive technique slightly overestimated the invasive COHb measurements and slightly underestimated the invasive MetHb measurements, there was close agreement between the two methods.

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Impaired erythrocyte methemoglobin reduction in sickle cell disease: dependence of methemoglobin reduction on reduced nicotinamide adenine dinucleotide content

Cited by 5 publications

References 0 publications

Effects of Erythrocyte Aging on Nitric Oxide and Nitrite Metabolism

Effects of Erythrocyte Aging on Nitric Oxide and Nitrite Metabolism

Simulation study of methemoglobin reduction in erythrocytes

Non‐invasive measurements of carboxyhemoglobin and methemoglobin in children with sickle cell disease

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