The basis of echinocytosis of the erythrocyte by glucose depletion

Abstract

Echinocytosis of erythrocytes by glucose depletion is attributed to adenosine triphosphate depletion, but its process still remains unknown. A mechanism of control of the erythrocyte shape has been previously proposed in which the anion exchanger Band 3, linked to flexible membrane skeleton, has a pivotal role. Recruitments of its inward facing (Band 3(i) ) and outward facing (Band 3(o) ) conformations contract and relax the membrane skeleton, thus promoting echinocytosis and stomatocytosis, respectively. The Band 3(o) /Band 3(i) equilibrium ratio increases with the increase of the Donnan equilibrium ratio, and preferential inward and outward transport by Band 3 of substrates slowly transported are echinocytogenic and stomatocytogenic, respectively. The mechanism suggests the following process. The major organic phosphate 2,3-bisphosphoglycerate is catabolized to lactate to form inorganic phosphate, 3-phosphoglycerate, and adenosine triphosphate. The last two products can be reversibly transformed into 1,3-bisphosphoglycerate and adenosine diphosphate by the glycolytic enzyme phosphoglycerate kinase, thus allowing 2,3-bisphosphoglycerate formation by 2,3-bisphosphoglycerate synthase/phosphatase. The catabolic and cyclic processes initially oppose echinocytosis by increasing the Donnan ratio and outward transport of slowly transported inorganic phosphate by Band 3 (its basic form is transported with a hydrogen ion). Echinocytosis occurs when inward transport of this product becomes predominant. This process can rationalize direct and indirect observations.

Purinergic signalling in endocrine organs

“…The authors suggest that defects in ATP-induced insulin signalling play a major role for the impaired glucose uptake in response to insulin treatment. Echinocytosis by glucose depletion, where erythrocytes shrink, has been attributed to ATP depletion, although other mechanisms may also be involved [593].…”

A Basis of the Crenation of Erythrocyte Ghosts by Electrolytes

“…Substrates slowly transported by band 3, preferentially inwardly and outwardly are echinocytogenic and stomatocytogenic, respectively. Recently, a process of echinocytosis by glucose depletion has been suggested based on this mechanism [28]. As was indicated, this process would be compatible with the reversal of ghost crenation by buffered isotonic saline by ATP-Mg 2+ complex, since ATP is hydrolyzed by a vanadatesensitive Mg 2+ -ATPase which would promote the stomatocytogenic outward transport of divalent P i with a hydrogen ion (H + ) (or monovalent P i ) by band 3 [18,[20][21][22].…”

A Basis of the Stomatocytoses of Erythrocytes by 1-Chloro-2, 4-Dinitrobenzene and Other Electrophilic Reagents

“…The band 3-based mechanism did not appear to be able to explain this stomatocytosis as well as other echinocytoses and stomatocytoses by other agents, including the echinocytosis by glucose depletion. However, recently, a process of echinocytosis by glucose depletion has been proposed based on this mechanism [5] and the following previous observations on ghosts and erythrocytes with other electrophilic reagents have drawn our attention, which led us to a second attempt to explain the stomatocytosis by CDNB by this mechanism. The structural analogue 1-fluoro-2,4-dinitrobenzene (FDNB) inhibited the band 3 anion exchange in resealed ghosts at a relatively low concentration (0.15-0.3 mM) [7][8][9][10].…”

“…This depletion is accompanied by a K + leakage, a stomatocytosis and a decrease of the erythrocyte deformability [2], and a negligible hemolysis [3] becoming prominent at a higher CDNB concentration (5 mM) [2,4]. This stomatocytosis was noticed during a survey of a literature in order to test the validity of a previously proposed band 3-based mechanism of control of the erythrocyte shape [5]. It appeared to be due to dinitrophenylations of membrane proteins and aminophospholipids since it was observed after cell washing [2].…”

“…Sphero-echinocytes formed by monopalmitoylphosphatidylcholine (0.07 mM) in a phosphate buffer saline supplemented with glucose are transformed to discocytes over a period of 7.5 h at 37 o C, which are transformed to stomatocytes by a selective extraction of monopalmitoylphosphatidylcholine molecular species in the outer leaflet with serum albumin [27]. This reversal transformation involves an inward translocation of a fraction of 0.13 of amphiphile molecular species in the outer leaflet which would be attributed to the increase of the band 3 o /band 3 i ratio by the outward transport of P i by band 3 promoted by glucose metabolism [5]. The echinocytosis by dimyristoylphosphatidylcholine, accompagnied by a vesiculation, was inhibited by TLCK at a stomatocytogenic concentration (4 mM) [13].…”