Familial phosphofructokinase deficiency is associated with a disturbed calcium homeostasis in erythrocytes

Ronquist, Gunnar; Rudolphi, Olle; Engström, Iva; Waldenström, Anders

doi:10.1046/j.1365-2796.2001.00780.x

Cited by 21 publications

(26 citation statements)

References 36 publications

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“…Halperin et al 32,33 showed that in the presence of transient, sublytic complement activation, potassium loss through the Gardos channel was essential in preventing hemolysis caused by colloid-osmotic swelling of the erythrocyte. Ronquist et al 34 have recently reported an increased Gardos channel activity in red cells of patients with myopathy and hemolytic anemia resulting from inherited phosphofructokinase (PFK) deficiency. In vitro normal red cells exposed to oxidants or to synthetic prostaglandins (PGE-2) showed abnormal activation of the Gardos channel, resulting in red cell dehydration.…”

Section: Discussionmentioning

confidence: 99%

Evidence for a protective role of the Gardos channel against hemolysis in murine spherocytosis

Franceschi

Rivera

Fleming

et al. 2005

Blood

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It has been shown that mice with complete deficiency of all 4.1R protein isoforms (4.1-/-) exhibit moderate hemolytic anemia, with abnormal erythrocyte morphology (spherocytosis) and decreased membrane stability. Here, we characterized the Gardos channel function in vitro and in vivo in erythrocytes of 4.1-/- mice. Compared with wild-type, the Gardos channel of 4.1-/- erythrocytes showed an increase in Vmax (9.75 +/- 1.06 vs 6.08 +/- 0.09 mM cell x minute; P < .04) and a decrease in Km (1.01 +/- 0.06 vs 1.47 +/- 1.02 microM; P < .03), indicating an increased sensitivity to activation by intracellular calcium. In vivo function of the Gardos channel was assessed by the oral administration of clotrimazole, a well-characterized Gardos channel blocker. Clotrimazole treatment resulted in worsening of anemia and hemolysis, with decreased red cell survival and increased numbers of circulating hyperchromic spherocytes and microspherocytes. Clotrimazole induced similar changes in 4.2-/- and band 3+/- mice, indicating that these effects of the Gardos channel are shared in different models of murine spherocytosis. Thus, potassium and water loss through the Gardos channel may play an important protective role in compensating for the reduced surface-membrane area of hereditary spherocytosis (HS) erythrocytes and reducing hemolysis in erythrocytes with cytoskeletal impairments.

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Section: Discussionmentioning

confidence: 99%

Evidence for a protective role of the Gardos channel against hemolysis in murine spherocytosis

Franceschi

Rivera

Fleming

et al. 2005

Blood

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“…Poorer antioxidant defense [8] and decreased accumulation of Ca in erythrocytes in the case of Mg deficiency [12] could also contribute to the decrease in ED. Both of these factors are associated with a decrease in the membrane flexibility; alterations of erythrocyte geometry; MELNIKOV, VIKULOV exhaustion of the ATP pool; and, eventually, a decrease in the cell deformability [7,[16][17][18].…”

Section: Resultsmentioning

confidence: 99%

Disorders in Magnesium Balance Decrease Erythrocyte Deformability in Athletes

Melnikov

Vikulov

2005

Hum Physiol

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Intense sports activity, especially in a warm climate, can cause Mg deficiency because of an imbalance between Mg consumption and its loss with urine and sweat [1,2]. Moreover, strenuous exercises can result in stress and overtraining [3], which disturb the Mg balance of the body [4]. A disturbance in the Mg balance influences various structures and functions of the body and leads to a decrease in physical working capacity [1]. However, the association between the Mg status and blood rheology in athletes is not clear.We have associated an increase in serum Mg with a decrease in the erythrocyte deformability (ED) in athletes [5]. This finding contradicts literature data on the favorable effect of Mg on ED [6,7]. It has been reported that Mg has a direct antioxidant effect on blood cells [8] and promotes accumulation of energyrich compounds in erythrocytes by affecting glycolysis (the phosphofructokinase activity and glucose phosphorylation) and glucose utilization [9]. Moreover, Mg is involved in maintaining a high level of cell hydration through inhibition of the K/Cl cotransport and activation of Na/K/Cl cotransport and Na/K ATPase [10,11]. Magnesium is also an antagonist of Ca and an activator of Ca ATPase [12]. The above effects of Mg can markedly influence the erythrocyte microrheology.Therefore, the present work was designed to study the relationship between Mg balance and erythrocyte rheology in athletes. METHODSThe study was performed with the participation of 45 highly qualified male athletes (masters and candidates of sport) training in different sports: track and field athletics, ski racing, wrestling, and weight lifting.Blood samples were taken in the morning (between 7:30 and 8:30 a.m.) on an empty stomach 24-36 h after a training session. Blood viscosity (BV), plasma viscosity (PV), and erythrocyte suspension viscosity at a hematocrit of 45% (ESV 45 ) were determined at τ = 0.5 Pa with a capillary viscometer ( t = 37 ± 0.5° C). The erythrocyte aggregation index was determined as described in [13]. Erythrocytes were washed twice, and a suspension of them with a hematocrit of 45% was combined with autologous plasma in the proportion 1 : 202. Nonaggregated erythrocytes were counted in a Goryaev chamber. Knowing the total erythrocyte concentration in the suspension, we calculated the percent of aggregated erythrocytes.Serum total protein was determined by the biuret reaction, serum protein fractions were assayed by paper electrophoresis, and fibrinogen was quantitated by Rutberg's technique. Serum total cholesterol (Ch), high density lipoprotein (HDL) Ch, and triglycerides (TG) were determined enzymatically. Reagent kits (Cormay, Poland) and a Shimadzu CL-770 spectrophotometer (Japan) were used. The acid resistance of erythrocytes to 0.002 N HCl was determined as described in [14]. The total working capacity was inferred from PWC 170 (a Ritm-5 bicycle ergometer).Serum Mg was determined spectrophotometrically with standard Lachema kits (Czech Republic), and Na was determined using ion-selective electrodes...

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“…] i is a feature of a number of diseases of the erythrocyte associated with hemolytic anemia such as sickle cell disease (SCD), ␤-thalassaemia, and familial phosphofructokinase (PFK) deficiency (103,315,340). In SCD-and PFK-deficient cells, Ca 2ϩ accumulates via increased entry through the red cell membrane, in a stochastic fashion in the case of sickled cells (209), likely causing a reduction in deformability (the ability for cells to change shape in response to flow) and leaving them prone to hemolysis (114, 315).…”

Section: Elevated [Ca 2ϩmentioning

confidence: 99%

“…In SCD-and PFK-deficient cells, Ca 2ϩ accumulates via increased entry through the red cell membrane, in a stochastic fashion in the case of sickled cells (209), likely causing a reduction in deformability (the ability for cells to change shape in response to flow) and leaving them prone to hemolysis (114, 315). Interestingly, in SCD a reduction in PMCA activity is likely to contribute to this Ca 2ϩ accumulation (114), whereas in PFK deficiency a compensatory increase in PMCA activity to clear the Ca 2ϩ leads to ATP depletion (315). There is also a suggestion that in an effort to prevent Ca 2ϩ overload, both SCD and ␤-thalassaemia erythrocytes are able to store Ca 2ϩ in endocytic inside-out vesicles, pumping it in via the PMCA (35, 208).…”

Section: Elevated [Ca 2ϩmentioning

confidence: 99%

The Plasma Membrane Calcium ATPasesand Their Role as Major New Players in Human Disease

Stafford

Wilson

Oceandy

et al. 2017

Physiological Reviews

110

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The Ca2+ extrusion function of the four mammalian isoforms of the plasma membrane calcium ATPases (PMCAs) is well established. There is also ever-increasing detail known of their roles in global and local Ca2+ homeostasis and intracellular Ca2+ signaling in a wide variety of cell types and tissues. It is becoming clear that the spatiotemporal patterns of expression of the PMCAs and the fact that their abundances and relative expression levels vary from cell type to cell type both reflect and impact on their specific functions in these cells. Over recent years it has become increasingly apparent that these genes have potentially significant roles in human health and disease, with PMCAs1-4 being associated with cardiovascular diseases, deafness, autism, ataxia, adenoma, and malarial resistance. This review will bring together evidence of the variety of tissue-specific functions of PMCAs and will highlight the roles these genes play in regulating normal physiological functions and the considerable impact the genes have on human disease.

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Familial phosphofructokinase deficiency is associated with a disturbed calcium homeostasis in erythrocytes

Cited by 21 publications

References 36 publications

Evidence for a protective role of the Gardos channel against hemolysis in murine spherocytosis

Evidence for a protective role of the Gardos channel against hemolysis in murine spherocytosis

Disorders in Magnesium Balance Decrease Erythrocyte Deformability in Athletes

The Plasma Membrane Calcium ATPasesand Their Role as Major New Players in Human Disease

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