Thymocyte K&lt;sup&gt;+&lt;/sup&gt;, Na&lt;sup&gt;+&lt;/sup&gt; and Water Balance During Dexamethasone- and Etoposide-Induced Apoptosis

Yurinskaya, Valentina E.; Moshkov, Alexey; Rozanov, Yuri M; Shirokova, A. V.; Vassilieva, Irina O.; Shumilina, Ekaterina; Läng, Florian; Volgareva, E V; Aa, Vereninov

doi:10.1159/000087727

Cited by 46 publications

(25 citation statements)

References 56 publications

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“…This inverse problem is much harder than finding concentrations from known parameters, and we approach it by trial and error. In the case of U937 cells, [Na] i , [K] i , [Cl] i , cell water content per unit of A , the pump coefficient β and OSOR were measured as described previously [11,12,13,14,15]. These data proved sufficient to find a unique set of parameters corresponding to the balanced state for a model that includes the pump, Na + , K + , Cl - channels and a single type of cotransport.…”

Section: Resultsmentioning

confidence: 99%

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Computation of Pump-Leak Flux Balance in Animal Cells

Vereninov

Yurinskaya²,

Model³

et al. 2014

Cell Physiol Biochem

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Background/Aims: Many vital processes in animal cells depend on monovalent ion transport across the plasma membrane via specific pathways. Their operation is described by a set of nonlinear and transcendental equations that cannot be solved analytically. Previous computations had been optimized for certain cell types and included parameters whose experimental determination can be challenging. Methods: We have developed a simpler and a more universal computational approach by using fewer kinetic parameters derived from the data related to cell balanced state. A file is provided for calculating unidirectional Na⁺, K⁺, and Cl^- fluxes via all major pathways (i.e. the Na/K pump, Na⁺, K⁺, Cl^- channels, and NKCC, KC and NC cotransporters) under a balanced state and during transient processes. Results: The data on the Na⁺, K⁺, and Cl^- distribution and the pump flux of K⁺ (Rb⁺) are obtained on U937 cells before and after inhibiting the pump with ouabain. There was a good match between the results of calculations and the experimentally measured dynamics of ion redistribution caused by blocking the pump. Conclusion: The presented approach can serve as an effective tool for analyzing monovalent ion transport in the whole cell, determination of the rate coefficients for ion transfer via major pathways and studying their alteration under various conditions.

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Section: Resultsmentioning

confidence: 99%

“…Salts were of analytical grade and were from Reachem (Russia). The experimental methods used in this work have been described in detail earlier [11,12,13,14,15]. Briefly, intracellular K + , Na + and Rb + content was analyzed by flame emission spectrometry, Cl - content was measured using 36 Cl - isotope.…”

Section: Methodsmentioning

confidence: 99%

Computation of Pump-Leak Flux Balance in Animal Cells

Vereninov

Yurinskaya²,

Model³

et al. 2014

Cell Physiol Biochem

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“…Eto induces apoptosis with shrinkage in rat thymocytes [31,32]. There is no specific inhibitory effect of Eto on shrinkage of U937 cells, as apoptosis with shrinkage was observed when we incubated U937 cells simultaneously with STS and Eto.…”

Section: Discussionmentioning

confidence: 99%

Potassium and Sodium Balance in U937 Cells During Apoptosis With and Without Cell Shrinkage

Yurinskaya

Goryachaya

Guzhova

et al. 2005

Cell Physiol Biochem

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Staurosporine (STS) and etoposide (Eto) induced apoptosis of the human histiocytic lymphoma cells U937 were studied to determine the role of monovalent ions in apoptotic cell shrinkage. Cell shrinkage, defined as cell dehydration, was assayed by measurement of buoyant density of cells in continuous Percoll gradient. The K⁺ and Na⁺ content in cells of different density fractions was estimated by flame emission analysis. Apoptosis was evaluated by confocal microscopy and flow cytometry of acridine orange stained cells, by flow DNA cytometry and by effector caspase activity. Apoptosis of U937 cells induced by 1 µM STS for 4 h was found to be paralleled by an increase in buoyant density indicating cell shrinkage. An increase in density was accompanied by a decrease in K⁺ content (from 1.1 to 0.78 mmol/g protein), which exceeded the increase in Na⁺ content (from 0.30 to 0.34 mmol/g) and resulted in a significant decrease of the total K⁺ and Na⁺ content (from 1.4 to 1.1 mmol/g). In contrast to STS, 50 µM Eto for 4 h or 0.8-8 µM Eto for 18-24 h induced apoptosis without triggering cell shrinkage. During apoptosis of U937 cells induced by Eto the intracellular K⁺/Na⁺ ratio decreased like in the cells treated with STS, but the total K⁺ and Na⁺ content remained virtually the same due to a decrease in K⁺ content being nearly the same as an increase in Na⁺ content. Apoptotic cell dehydration correlated with the shift of the total cellular K⁺ and Na⁺ content. There was no statistically significant decrease in K⁺ concentration per cell water during apoptosis induced by either Eto (by 13.5%) or STS (by 8%), whereas increase in Na⁺ concentration per cell water was statistically significant (by 27% and 47%, respectively). The data show that apoptosis can occur without cell shrinkage-dehydration, that apoptosis with shrinkage is mostly due to a decrease in cellular K⁺ content, and that this decrease is not accompanied by a significant decrease of K⁺ concentration in cell water.

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“…However, this is not necessarily the case as a significant ionic imbalance has been shown to occur under a variety of apoptotic conditions. In rat thymocytes treated with dexamethasone or etoposide [105] or U-937 cells treated with staurosporine [106], apoptotic cell shrinkage was paralleled by a decrease in intracellular potassium that exceeded the increase in intracellular sodium, thus resulting in a significant decrease in total sodium and potassium content. In contrast, when U-937 cells, that showed an ionic imbalance with staurosporine, were treated with etoposide to induce apoptosis, the intracellular potassium to sodium ratio decreased, but the total sodium and potassium content remained virtually the same.…”

Section: Sodium As a Signal During Apoptosismentioning

confidence: 96%

Cell shrinkage and monovalent cation fluxes: Role in apoptosis

Bortner

Cidlowski

2007

Archives of Biochemistry and Biophysics

230

193

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The loss of cell volume or cell shrinkage has been a morphological hallmark of the programmed cell death process known as apoptosis. This isotonic loss of cell volume has recently been term apoptotic volume decrease or AVD to distinguish it from inherent volume regulatory responses that occurs in cells under anisotonic conditions. Recent studies examining the intracellular signaling pathways that result in this unique cellular characteristic have determined that a fundamental movement of ions, particularly monovalent ions, underlie the AVD process and plays an important role on controlling the cell death process. An efflux of intracellular potassium was shown to be a critical aspect of the AVD process, as preventing this ion loss could protect cells from apoptosis. However, potassium plays a complex role as a loss of intracellular potassium has also been shown to be beneficial to the health of the cell. Additionally, the mechanisms that a cell employs to achieve this loss of intracellular potassium vary depending on the cell type and stimulus used to induce apoptosis, suggesting multiple ways exist to accomplish the same goal of AVD. Additionally, sodium and chloride have been shown to play a vital role during cell death in both the signaling and control of AVD in various apoptotic model systems. This review examines the relationship between this morphological change and intracellular monovalent ions during apoptosis.

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Thymocyte K<sup>+</sup>, Na<sup>+</sup> and Water Balance During Dexamethasone- and Etoposide-Induced Apoptosis

Cited by 46 publications

References 56 publications

Computation of Pump-Leak Flux Balance in Animal Cells

Computation of Pump-Leak Flux Balance in Animal Cells

Potassium and Sodium Balance in U937 Cells During Apoptosis With and Without Cell Shrinkage

Cell shrinkage and monovalent cation fluxes: Role in apoptosis

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