Transformation and restoration of biconcave shape of human erythrocytes induced by amphiphilic agents and changes of ionic environment

Deüticke, B.

doi:10.1016/0005-2736(68)90078-3

Cited by 437 publications

(189 citation statements)

References 13 publications

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“…The nonspecific interaction of local anesthetics and phenothiazines with membranes is not specific to yeast cells because similar membrane interactions have been proposed following morphologic analysis of erythrocyte cells (Deuticke 1968;Sheetz and Singer 1974). These interactions simply may be due to the intercalation of the amphiphilic drugs along the orientation of amphiphilic phospholipids in the lipid bilayer.…”

Section: Discussionmentioning

confidence: 94%

“…The inner leaflet of the yeast plasma membrane is enriched in phosphatidylethanolamine (PE), phosphatidylinositol (PI), and phosphatidylserine (PS) (van der Rest et al 1995); this composition is similar to that of erythrocyte membranes (Op den Kamp 1979). Morphologic studies of erythrocytes suggest that the positively charged cationic amphiphiles, including local anesthetics and phenothiazines, preferentially intercalate into the inner leaflet enriched in the negative-charged PI and PS (Deuticke 1968;Sheetz and Singer 1974). Thus, cationic amphiphiles would preferentially and nonspecifically intercalate into the inner leaflets of the yeast lipid bilayer via electrostatic interactions with anionic phospholipids (Figure 8).…”

Section: Discussionmentioning

confidence: 99%

“…However, in contrast to the effects caused by cationic TMA12, anionic SDS does not inhibit translation initiation (Uesono et al 2008), and additional glucose does not alleviate the SDS-associated growth inhibition ( Figure 3A). Therefore, anionic amphiphiles, which are considered to intercalate into outer leaflets (Deuticke 1968), are unlikely to induce glucose starvation. This simply suggests that cationic amphiphiles efficiently inhibit Hxts by penetrating into the open space of the oscillation area at the inner leaflet, but anionic amphiphiles do not because the area at the outer leaflets has no space if the Hxts importing extracellular hexoses usually exist as the outward-facing form ( Figure 8A, low drugs).…”

Section: Discussionmentioning

confidence: 99%

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Local Anesthetics and Antipsychotic Phenothiazines Interact Nonspecifically with Membranes and Inhibit Hexose Transporters in Yeast

et al. 2016

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Action mechanisms of anesthetics remain unclear because of difficulty in explaining how structurally different anesthetics cause similar effects. In Saccharomyces cerevisiae, local anesthetics and antipsychotic phenothiazines induced responses similar to those caused by glucose starvation, and they eventually inhibited cell growth. These drugs inhibited glucose uptake, but additional glucose conferred resistance to their effects; hence, the primary action of the drugs is to cause glucose starvation. In hxt 0 strains with all hexose transporter (HXT) genes deleted, a strain harboring a single copy of HXT1 (HXT1s) was more sensitive to tetracaine than a strain harboring multiple copies (HXT1m), which indicates that quantitative reduction of HXT1 increases tetracaine sensitivity. However, additional glucose rather than the overexpression of HXT1/2 conferred tetracaine resistance to wild-type yeast; therefore, Hxts that actively transport hexoses apparently confer tetracaine resistance. Additional glucose alleviated sensitivity to local anesthetics and phenothiazines in the HXT1m strain but not the HXT1s strain; thus, the glucose-induced effects required a certain amount of Hxt1. At low concentrations, fluorescent phenothiazines were distributed in various membranes. At higher concentrations, they destroyed the membranes and thereby delocalized Hxt1-GFP from the plasma membrane, similar to local anesthetics. These results suggest that the aforementioned drugs affect various membrane targets via nonspecific interactions with membranes. However, the drugs preferentially inhibit the function of abundant Hxts, resulting in glucose starvation. When Hxts are scarce, this preference is lost, thereby mitigating the alleviation by additional glucose. These results provide a mechanism that explains how different compounds induce similar effects based on lipid theory.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Local Anesthetics and Antipsychotic Phenothiazines Interact Nonspecifically with Membranes and Inhibit Hexose Transporters in Yeast

et al. 2016

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“…They can be engendered by most forms of physical abuse, and most of all by lipophilic drugs or other molecules that partition into the membrane. Two types of shape transformation can be recognized: in general (Deuticke, 1968) anionic solutes generate echinocytes, with rather large protuberances distributed over the cell surface, and cationic species give rise to stomatocytes, or smooth cup shapes. Exposure of the cell to two ligands, one of either type, can lead to a cancellation of the two effects, with retention of the discoid shape.…”

Section: Metabolic Regulation Of Cell Shapementioning

confidence: 99%

The red cell membrane and its cytoskeleton

Gratzer¹

1981

Biochemical Journal

127

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“…1) upon variation of the electrolyte concentration [1][2][3][4][5][6][7], increase of the medium's pH [7][8][9][10][11][12], addition of amphiphiles and other agents [1,[13][14][15][16][17][18], and changes in temperature [19,20]. A general correlation was found between the erythrocyte shape and the transmembrane electric potential [21][22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

On the mechanism of stomatocyte–echinocyte transformations of red blood cells: experiment and theoretical model

Tachev¹,

Danov²,

Kralchevsky³

2004

Colloids and Surfaces B: Biointerfaces

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This study represents an attempt to achieve a better understanding of the stomatocyte-echinocyte transition in the shape of red blood cells. We determined experimentally the index of cell shape at various ionic strengths and osmolarities for native and trypsin-treated human erythrocytes. For every given composition of the outer phase, we calculated the ionic strength in the cells and the transmembrane electric potential using a known theoretical model. Next, we described theoretically the electric double layers formed on both sides of the cell membrane, and derived expressions for the tensions of the two membrane leaflets. Taking into account that the cell-shape index depends on the tension difference between the two leaflets, we fitted the experimental data with the constructed physicochemical model. The model, which agrees well with the experiment, indicates that the tension difference between the two leaflets is governed by the different adsorptions of counterions at the two membrane surfaces, rather than by the direct contribution of the electric double layers to the membrane tension. Thus, with the rise of the ionic strength, the counterion adsorption increases stronger at the outer leaflet, whose stretching surface pressure becomes greater, and whose area expands relative to that of the inner leaflet. Hence, there is no contradiction between the bilayer-couple hypothesis and the electric double layer theory, if the latter is upgraded to account for the effect of counterion-adsorption on the membrane tension. The developed quantitative model can be applied to predict the shape index of cells upon a stomatocyte-discocyte-echinocyte transformation at varying composition of the outer medium.

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Transformation and restoration of biconcave shape of human erythrocytes induced by amphiphilic agents and changes of ionic environment

Cited by 437 publications

References 13 publications

Local Anesthetics and Antipsychotic Phenothiazines Interact Nonspecifically with Membranes and Inhibit Hexose Transporters in Yeast

Local Anesthetics and Antipsychotic Phenothiazines Interact Nonspecifically with Membranes and Inhibit Hexose Transporters in Yeast

The red cell membrane and its cytoskeleton

On the mechanism of stomatocyte–echinocyte transformations of red blood cells: experiment and theoretical model

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