Mechanisms in Volume Regulation in Ehrlich Ascites Tumor Cells

Hoffmann, Else K.; Lambert, Ian Henry; Simonsen, Leif

doi:10.1159/000173164

Cited by 28 publications

(30 citation statements)

References 55 publications

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“…2 illustrates clearly that A6 cells demonstrate a regulatory volume decrease (RVD) as described for other epithelial cell types (Hoffmann et al, 1988;Welling and Linshaw, 1988;Kirk et al, 1987). Yet, the most striking result obtained from this type of experiment was the failure of A6 cells to restore their volume to control after establishing isoosmofic conditions (period III).…”

Section: Resultsmentioning

confidence: 69%

“…To keep the osmolality of the amino acid containing solution identical to the 250-ISO and 140-HYPO solutions, we had to reduce the CI-concentration. As Cl-plays an important role in volume regulatory processes of most cells (Hoffmann et al, 1988) we performed experiments with low C1--containing solutions (CI-ISO and C1-HYPO). Our result showed that the reduction of CI-in the bathing solution impaired volume regulation.…”

Section: Oomentioning

confidence: 99%

“…This decline phenomenon has been termed regulatory volume decrease (RVD). In many epithelial (Kirk, Schafer, and DiBona, 1987;Lopes and Guggino, 1987;McCarty and O'Neil, 1991) and nonepithelial cells (Hoffman, Lambert, and Simonsen, 1986) the readjustment of cell volume is achieved by the loss of KC1 either through ion conductive channels or by means of a coupled KCI cotransport system (Hoffmann, Lambert, and Simonsen, 1988). However, the mechanisms which trigger the activation of these pathways are still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Regulatory volume decrease in cultured kidney cells (A6): role of amino acids.

Smet

Simaels

Declercq

et al. 1995

The Journal of General Physiology

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Volume regulation was studied in A6 epithelia grown on permeable supports by measuring cell thickness (To) while simultaneously recording short circuit current (Ix) and tmalsepithelial conductance (Gt). Lowering the tonicity of the basolateral solution (Wb) from 250 or 215 to 140 mOsm/kg elicited a rapid rise in Tc followed by a regulation of the cell volume towards control. This decrease in Tc displays the characteristics of the regulatory volume decrease (RVD). Upon restoring the isoosmotic conditions, T~ decreased rapidly below its control value. A post RVD regulatory volume increase (RVI) as described for other cell types was not observed. The subsequent reduction of the basolateral osmolality increased Tc to the level recorded at the end of the first hypoosmotic pulse. Because cell content was not altered during the isoosmotic period the second hypoosmotic challenge was isotonic with the cell and did therefore not evoke an RVD. However, the cell did not lose its ability to volume regulate since an RVD could be elicited by further reduction of 1rb from 140 to 100 mOsm/kg. The possibility of an involvement of amino acids in the RVD was tested. The amount of amino acids in the cell as well as excreted in the bath was determined by amino acid analysis. Millimolar concentrations of threonine, serine, alanine, glutamate, glycine and aspartate were found in the cell extract. The cellular amino acid concentration was 28.8 -+ 0.4 mM. The amounts of glycine, aspartate and glutamate excreted from the cell during the hypotonic treatment were significantly larger than in control conditions. The excretion of these amino acids during hypotonicity decreased the cellular amino acid concentration by 8.4 -+ 0.2 mM. This quantity cannot completely account for the RVD during the first hypotonic challenge. The addition of glycine, aspartate and glutamate to the bathing solutions, although used at concentrations higher than intracellularly, did not reduce RVD. On the contrary, this maneuver increased the amplitude of the RVD following both hypoosmotic pulses. This result suggests a stimulatory role of the amino acids on the processes responsible for the RVD.

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Section: Resultsmentioning

confidence: 69%

Section: Oomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Regulatory volume decrease in cultured kidney cells (A6): role of amino acids.

Smet

Simaels

Declercq

et al. 1995

The Journal of General Physiology

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“…Cells activate VSOR 1 Cl Ϫ channels in response to an increase in cell volume (11)(12)(13). These channels are also found to be activated under conditions in which cell volume is constant (14 -16), providing further evidence for their participation in a variety of functions other than cell volume regulation.…”

mentioning

confidence: 82%

NAD(P)H Oxidase-derived H2O2 Signals Chloride Channel Activation in Cell Volume Regulation and Cell Proliferation

Varela

Simón

Riveros

et al. 2004

Journal of Biological Chemistry

141

136

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Cellular swelling triggers the activation of Cl؊ channels (volume-sensitive outwardly rectifying (VSOR) Cl ؊ channels) in many cell types. Ensuing regulatory volume decrease has been considered the primary function of these channels. However, Cl ؊ channels, which share functional properties with volume-sensitive Cl ؊ channels, have been shown to be involved in other physiological processes, including cell proliferation and apoptosis, raising the question of their physiological roles and the signal transduction pathways involved in their activation. Here we report that exogenously applied H 2 O 2 elicited VSOR Cl ؊ channel activation. Furthermore, activation of these channels was found to be coupled to NAD(P)H oxidase activity. Also, epidermal growth factor, known to increase H 2 O 2 production, activated Cl ؊ channels with properties identical to swelling-sensitive Cl ؊ channels. It is concluded that NAD(P)H oxidasederived H 2 O 2 is the common signal transducing molecule that mediates the activation of these ubiquitously expressed anion channels under a variety of physiological conditions.

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“…Effect of glutamine on urea synthesis from NH,Cl under isotonic and hypotonic perfusion conditions. In hypotonic perfusion, the NaCl concentration of the Krebs- (8) NH,Cl (0.5 mM) + glutamine (0.6 mM) 2.11 0.14(6) 1.14 & 0.12 (6) on liver mass (i.e. an increase by 4.0 f 0.5% n = 7) is fully reversible upon withdrawal of glutamine from the influent perfusate; there is even an undershoot in liver mass, followed by a slow increase.…”

Section: Effect Of Glutamine On Liver-cell Volumementioning

confidence: 99%

Interactions between glutamine metabolism and cell‐volume regulation in perfused rat liver

Häussinger

Läng

Bauers

et al. 1990

European Journal of Biochemistry

104

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1. In the presence of near-physiological glutamine concentrations, exposure of perfused rat liver to hypotonic perfusion media switched glutamine balance across the liver from net release to net uptake. This was due to both stimulation of flux through glutaminase and inhibition of flux through glutamine synthetase. Conversely, during exposure to hypertonic media, net glutamine release from the liver increased due to inhibition of glutaminase flux and slight stimulation of flux through glutamine synthetase. The effect of perfusate osmolarity on glutaminase flux was observed at an NH4C1 concentration (0.5 mM) sufficient for near-maximal ammonia stimulation of glutaminase. This indicates the involvement of different mechanisms of glutaminase flux control by extracellular osmolarity changes and ammonia. The effects of anisotonicity on flux through glutamine-metabolizing enzymes were fully reversible. Glutamine (0.6 mM) stimulated urea synthesis from NH4Cl (0.5 mM) during hypotonic and normotonic conditions.2. Exposure to hypotonic and hypertonic media led, after initial liver-cell swelling and shrinkage, respectively to volume-regulatory K + fluxes which largely restored the initial liver-cell volume despite the continuing osmotic challenge. Even after completion of cell-volume regulatory K + fluxes, the effects of perfusate osmolarity on hepatic glutamine metabolism persisted. This indicates that in anisotonicity the liver cell is left in an altered metabolic state, even after completion of volume-regulatory responses.3. During perfusion with isotonic media, addition of glutamine (3 mM) led to an increase of liver mass by about 4% within 2 min, which was accompanied by a net K + uptake by the liver. Thereafter, the new steady state of increased liver mass was maintained throughout glutamine infusion. When the liver mass had reached this new steady state, a net release of K from the liver of about 3 pmol/g liver was observed during the following 10 min.Withdrawal of glutamine was followed by a slow reuptake of K + and the liver mass returned to its initial value. Following exposure to glutamine (3 mM), the intracellular glutamine concentration (as calculated from glutamine tissue levels, taking into account the extracellular space determined with the [3H]inulin technique) rose from about 1 mM to 30-35 mM within about 12 min, indicating a 10-12-fold concentrative uptake of glutamine into the liver cells and an osmotic challenge for the hepatocyte. When intracellular glutamine had reached its steady-state concentration, net K + efflux from the liver was also terminated. 4. It is concluded that (a) hepatic glutamine metabolism is under the control of liver-cell volume and/or volume-regulatory responses, thereby involving flux changes through glutaminase and glutamine synthetase, i.e. alterations of intercellular glutamine cycling; (b) volume-regulatory mechanisms may be signals for switching carbohydrate utilization to glutamine utilization as respiratory fuel and vice versa; and (c) the concentrative uptake of glutami...

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Mechanisms in Volume Regulation in Ehrlich Ascites Tumor Cells

Cited by 28 publications

References 55 publications

Regulatory volume decrease in cultured kidney cells (A6): role of amino acids.

Regulatory volume decrease in cultured kidney cells (A6): role of amino acids.

NAD(P)H Oxidase-derived H2O2 Signals Chloride Channel Activation in Cell Volume Regulation and Cell Proliferation

Interactions between glutamine metabolism and cell‐volume regulation in perfused rat liver

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