Osmotic effects of protein polymerization: Analysis of volume changes in sickle cell anemia red cells following deoxy-hemoglobin S polymerization

Lew, Virgilio L.; Bookchin, Robert M.

doi:10.1007/bf01872739

Cited by 22 publications

(15 citation statements)

References 40 publications

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“…Vital signs including systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate, and temperature, and laboratory values including white blood cell count, hemoglobin, hematocrit, platelet count, sedimentation rate, Na, K, Cl, CO 2 , BUN, creatinine, glucose, AST, ALT, alkaline phosphatase, and total bilirubin levels also did not differ statistically between the two subgroups. The rate of admission for NFEDV was 19% for the NFEDV group and 44% for the FEDV group (P ¼ 0.61, 2 ).…”

Section: Resultsmentioning

confidence: 96%

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Serum ionized magnesium levels and ionized calcium‐to‐magnesium ratios in adult patients with sickle cell anemia

et al. 2004

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Low levels of total magnesium in sickle cell erythrocytes have been linked to increased sickling due to cell dehydration. We tested the null hypothesis that adult sickle cell anemia (SCA) patients have the same serum level of ionized Mg (Mg 2+ ) and Ca 2+ /Mg 2+ ratio as healthy African Americans (AA) and healthy Caucasians (CAUC). We measured serum Mg 2+ and ionized calcium (Ca 2+ ) with ion-selective electrodes and calculated the serum Ca 2+ /Mg 2+ ratios in patients with SCA and control groups (AA and CAUC). Seventyfour SCA patients and 61 controls were compared. SCA patients had significantly (P < 0.001) lower levels of serum Mg 2+ (0.52 ± 0.05) compared to healthy AA (0.57 ± 0.04) and CAUC (0.62 ± 0.03). Eighty-six percent of the adult SCA patients had serum Mg 2+ levels below the mean for the AA group, and 96% of SCA patients were above the AA group's mean serum Ca 2+ /Mg 2+ . Of the SCA patients studied, 25.6% (95% CI, 16.2-37.2%) had serum Mg 2+ levels below the racially adjusted lower limit of normal and 50% (95% CI, 38.1-61.9%) were above the upper limit of serum Ca 2+ /Mg 2+ for AA controls. By measuring serum Mg 2+ and Ca 2+ , we were able to define a subset of SCA patients with hypomagnesemia and elevated Ca 2+ /Mg 2+ ratios, who may benefit from magnesium supplementation. Am.

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Section: Resultsmentioning

confidence: 96%

“…The kinetics of polymerization depends upon high concentrations of HbS, as a consequence of dehydration of SCA RBCs [1][2][3]. Homeostasis of RBC volume in SCA is controlled in part by a dynamic equilibrium between ionic, free calcium (Ca 2+ ) and magnesium (Mg 2+ ).…”

Section: Introductionmentioning

confidence: 99%

Serum ionized magnesium levels and ionized calcium‐to‐magnesium ratios in adult patients with sickle cell anemia

et al. 2004

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“…Along those lines, activation of Ca 2+ -sensitive K + channels participates in the cell shrinkage and deformation of desoxygenized sickle cells [46][47][48][49][50] which are highly sensitive to stress-induced eryptosis [21]. Moreover, accelerated eryptosis has previously been demonstrated in several further anemic conditions, including beta-thalassemia or glucose-6-phosphate dehydrogenase (G6PD)-deficiency [21], phosphate depletion [30], iron deficiency anemia [31] and intoxication with lead [40] or mercury [39].…”

Section: Discussionmentioning

confidence: 99%

Suicidal Erythrocyte Death Following Cellular K<sup>+</sup> Loss

Schneider

Nicolay

Föller

et al. 2007

Cell Physiol Biochem

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Hallmarks of apoptosis include cell shrinkage, which is at least partially due to cellular K⁺ loss. The decline of cellular K⁺ concentration has been suggested to participate in the triggering of apoptosis. Suicidal erythrocyte death or eryptosis is triggered by increased cytosolic Ca²⁺ activity leading to activation of Ca²⁺-sensitive K⁺ channels with subsequent cellular K⁺ loss and cell shrinkage, and to Ca²⁺-sensitive scambling of the cell membrane with subsequent phosphatidylserine (PS) exposure at the cell surface. Phosphatidylserine exposing erythrocytes are recognized by macrophages, engulfed, degraded and thus cleared from circulating blood. The present study explored whether cellular loss of K⁺ and/or cell shrinkage actively participate in the triggering of cell membrane phospholipid scrambling. Cellular K⁺ loss was achieved by treatment of human erythrocytes with the K⁺ ionophore valinomycin (1 nM) at different extracellular K⁺ concentrations (5-125 mM) and osmolarities (300-550m Osm). Cell volume was estimated from forward scatter and PS exposure from annexin V binding in FACS analysis. Treatment with 1 nM valinomycin indeed decreased forward scatter and increased annexin V binding. The effect was significantly blunted in the presence of staurosporine (1 µM). Increase of extracellular K⁺ concentration gradually blunted the decrease of forward scatter but inhibited annexin V binding only at extracellular K⁺ concentrations ??75 mM. An increase of extracellular osmolarity (+150 mM or 250 mM sucrose) reversed the protective effect of 75 mM KCl during valinomycin treatment. A correlation between forward scatter and annexin binding at different osmolarities and K⁺ concentrations suggests that the cellular K⁺ content determines the rate of suicidal erythrocyte death primarily through its influence on cell volume.

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“…The subsequent hyperpolarisation of the cell membrane would drive Cl -out of the cell and the cellular loss of KCl with osmotically obliged water thus lead to cell shrinkage [50,51]. Loss of cellular K + is considered a requirement of apoptosis in several cell types [52][53][54][55][56][57][58] and activation of Ca 2+ sensitive K + channels participates in the cell shrinkage and deformation of desoxygenized sickle cells [48,49,[59][60][61] which have most recently been shown to be highly sensitive to eryptosis following osmotic shock or oxidative stress [62]. However, exposure for 6 hours to 3 µM methylglyoxal had little effect on forward scatter, suggesting that at those concentrations and exposure times methylglyoxal did not substantially increase cytosolic Ca 2+ activity.…”

Section: Discussionmentioning

confidence: 99%

Stimulation of Suicidal Erythrocyte Death by Methylglyoxal

Nicolay

Schneider

Niemoeller

et al. 2006

Cell Physiol Biochem

217

178

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Diabetes increases the percentage of circulating erythrocytes exposing phosphatidylserine (PS) at the cell surface. PS-exposing erythrocytes are recognized, bound, engulfed and degraded by macrophages. Thus, PS exposure, a feature of suicidal erythrocyte death or eryptosis, accelerates clearance of affected erythrocytes from circulating blood. Moreover, PS-exposing erythrocytes bind to the vascular wall thus interfering with microcirculation. The present study explored mechanisms involved in the triggering of PS exposure by methylgloxal, an extra- and intracellular metabolite which is enhanced in diabetes. PS exposure, cell size and cytosolic Ca²⁺-activity after methylglyoxal treatment were measured by FACS analysis of annexin V binding, forward scatter and Fluo-3-fluorescence, respectively, and it was shown that the treatment significantly enhanced the percentage of PS-exposing erythrocytes at concentrations (0.3 µM) encountered in diabetic patients. Surprisingly, methylglyoxal did not significantly increase cytosolic Ca²⁺ concentration, and at concentrations up to 3 µM, did not decrease the forward scatter. Instead, exposure to methylglyoxal inhibited glycolysis thus decreasing ATP and GSH concentrations. In conclusion, methylglyoxal impairs energy production and anti-oxidative defense, effects contributing to the enhanced PS exposure of circulating erythrocytes and eventually resulting in anemia and deranged microcirculation.

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Osmotic effects of protein polymerization: Analysis of volume changes in sickle cell anemia red cells following deoxy-hemoglobin S polymerization

Cited by 22 publications

References 40 publications

Serum ionized magnesium levels and ionized calcium‐to‐magnesium ratios in adult patients with sickle cell anemia

Serum ionized magnesium levels and ionized calcium‐to‐magnesium ratios in adult patients with sickle cell anemia

Suicidal Erythrocyte Death Following Cellular K<sup>+</sup> Loss

Stimulation of Suicidal Erythrocyte Death by Methylglyoxal

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