Signalling Mechanisms Involved in Volume Regulation of Intestinal Epithelial Cells

Wijk, Thea van der; Tomassen, Sebastian F.B.; Jonge, Hugo R. de; Tilly, Ben C.

doi:10.1159/000016359

Cited by 34 publications

(32 citation statements)

References 47 publications

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“…MAP kinase inhibitors did not alter RVD upon hypoosmolarity in intestinal epithelial cells [54] and it is therefore suggested that osmosignalling towards RVD is cell-specific. The exact nature of the residual nonp38 MAPK -dependent RVD in liver still mains to be elucidated.…”

Section: Discussionmentioning

confidence: 91%

Role of p38<sup>MAPK</sup> in Cell Volume Regulation of Perfused Rat Liver

Dahl

Schliess

Graf

et al. 2001

Cell Physiol Biochem

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In perfused rat liver, hypoosmotic exposure (225 mosmol/L) leads to a volume-regulatory decrease by release of K⁺, Cl^- and HCO₃^- through Ba²⁺-, DIDS- and quinidine-sensitive ion channels. The underlying signal transduction mechanisms, however, are unknown. As hypoosmotic hepatocyte swelling leads to a rapid activation of extracellular signal regulated kinases (Erks) and of p38^MAPK, the role of mitogen-activated protein kinases (MAPK) and PI-3-kinase in mediating the RVD in perfused rat liver was studied. The presence of the MEK inhibitor PD 098 059, which blocks the hypoosmotic activation of Erks, had no effect on the extent and time course of cell volume regulatory K⁺ efflux. However, inhibitors of p38^MAPK such as SB 203 580 and PD 169 316, but not their inactive analogue SB 202 474, significantly delayed and diminished the volume-regulatory K⁺ efflux. Accordingly, in presence of these p38^MAPK inhibitors, the hepatocytes remained in a more swollen state after completion of RVD. Inhibition of hypoosmotic Erk activation by pertussis or cholera toxin, erbstatin or genistein had no effect on RVD by hypoosmolarity. Likewise, neither inhibition of PI-3-kinase by wortmannin or LY 294 002 nor inhibition of S 6 phosphorylation by rapamycin nor protein kinase inhibition by H-7, H-89 or KT 5823 led to a significant change of RVD upon hypoosmolarity. The amount and time course of K⁺ release by oxidative stress upon addition of t-BOOH or H₂O₂ remained unaffected by inhibition of p38^MAPK by SB 203 580, suggesting a specific inhibition of RVD-dependent K⁺ release by this inhibitor. The findings suggest that swelling-induced activation of p38^MAPK, but not of Erks and PI-3-kinase, is involved in RVD in liver, whereas p38^MAPK is apparently not involved in the net K⁺ release induced by oxidative stress.

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Section: Discussionmentioning

confidence: 91%

Role of p38<sup>MAPK</sup> in Cell Volume Regulation of Perfused Rat Liver

Dahl

Schliess

Graf

et al. 2001

Cell Physiol Biochem

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“…Stretch-activated ion channels (SAC) may be activated as a direct response to membrane stretch. [89], whereas in human cervical cancer cells hypotonicity-induced elevation of Ca i by entry from the extracellular medium is a prerequisite for normal RVD [90]. In the latter cell type the hypotonicity-induced Ca 2+ signalling and the swelling-dependent Cl -and taurine release were found to require myosin light chain kinase (MLCK) activity, but did not correlate with MLC phosphorylation, which implies that MLCK controls Ca 2+ signalling by an MLC phosphorylation-independent mechanism [90].…”

Section: Intracellular Calcium (Ca I ) Levelsmentioning

confidence: 93%

“…This indicates that in these cells the swelling-induced ATP release is independent of RVDC activation. Furthermore auto/paracrine ATP signaling does not activate RVDC in human intestine 407 cells, however, the ATP signaling via P2Y receptors is responsible for swellinginduced Erk1/2 activation [89,157] and can potentiate the rise of Ca i in response to hypotonic swelling by stimulating cellular Ca 2+ entry via volume-sensitive cation channels and by release from intracellular stores [86]. In rat hepatocytes and HTC hepatoma cells, the volumesensitive ATP release is inhibited by Gd 3+ .…”

Section: Autocrine Regulation Of Rvd By Hormones and Transmittersmentioning

confidence: 95%

“…This leads to surface enlargement at the expense of the microvillar membrane, to ion and water fluxes between the two compartments due to shortening of the microvillar diffusion barrier and to volume regulatory ion fluxes [256]. (v) The cytoskeleton can participate in macromolecular crowding (see bolw) and (vi) it is involved in the regulation of the exocytotic release of organic osmolytes [110]and propably ATP [89]. (vii) Cytoskeletal remodeling might also create local osmotic gradients, leading to osmotically driven water fluxes [211,257] and (viii) it can generate mechanical forces by promoting actin-myosin interaction [39].…”

Section: Cytoskeleton and Protein To Membrane Transpositionmentioning

confidence: 99%

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Mechanisms Sensing and Modulating Signals Arising From Cell Swelling

Jakab

Fuerst

Gschwentner

et al. 2002

Cell Physiol Biochem

125

100

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Cell volume alterations are involved in numerous cellular events like epithelial transport, metabolic processes, hormone secretion, cell migration, proliferation and apoptosis. Above all it is a need for every cell to counteract osmotic cell swelling in order to avoid cell damage. The defence against excess cell swelling is accomplished by a reduction of the intracellular osmolarity by release of organic- or inorganic osmolytes from the cell or by synthesis of osmotically less active macromolecules from their specific subunits. De-spite the large amount of experimental data that has accumulated, the intracellular mechanisms underlying the sensing of cell volume perturbations and the activation of volume compensatory processes, commonly summarized as regulatory volume decrease (RVD), are still only partly revealed. Moving into this field opens a complex scenario of molecular rearrangements and interactions involving intracellular messengers such as calcium, phosphoinositides and inositolphosphates as well as phosphoryla-tion/dephosphorylation processes and cytoskeletal reorganization with marked cell type- and tissue specific variations. Even in one and the same cell type significant differences regarding the activated pathways during RVD may be evident. This makes it virtually im-possible to unambigously define common sensing- and sinaling pathways used by differ-ent cells to readjust their celll volume, even if all these pathways converge to the activa-tion of comparatively few sets of effectors serving for osmolyte extrusion, including ion channels and transporters. This review is aimed at providing an insight into the manifold cellular mechanisms and alterations occuring during cell swelling and RVD.

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“…Most cell types respond immediately to osmotic changes by activating plasma membrane transport pathways leading to net accumulation (upon hyperosmotic stress) or loss (upon hyposmotic stress) of osmotically active intracellular solutes (11,43). The mechanism(s) whereby altered intracellular osmolarity interferes with physiological mammalian cell functions such as proliferation and differentiation is(are) poorly understood.…”

Section: Effect Of Changes In Extracellular Osmosis On Cell Growth-mentioning

confidence: 99%

Hyposmotic Stress Induces Cell Growth Arrest via Proteasome Activation and Cyclin/Cyclin-dependent Kinase Degradation

Tao¹,

Rott

Lowe

et al. 2002

Journal of Biological Chemistry

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Ordered cell cycle progression requires the expression and activation of several cyclins and cyclin-dependent kinases (Cdks). Hyperosmotic stress causes growth arrest possibly via proteasome-mediated degradation of cyclin D1. We studied the effect of hyposmotic conditions on three colonic (Caco2, HRT18, HT29) and two pancreatic (AsPC-1 and PaCa-2) cell lines. Hyposmosis caused reversible cell growth arrest of the five cell lines in a cell cycle-independent fashion, although some cell lines accumulated at the G 1 /S interface. Growth arrest was followed by apoptosis or by formation of multinucleated giant cells, which is consistent with cell cycle catastrophe. Hyposmosis dramatically decreased Cdc2, Cdk2, Cdk4, cyclin B1, and cyclin D3 expression in a time-dependent fashion, in association with an overall decrease in cellular protein synthesis. However, some protein levels remained unaltered, including cyclin E and keratin 8. Selective proteasome inhibition prevented Cdk and cyclin degradation and reversed hyposmotic stress-induced growth arrest, whereas calpain and lysosome enzyme inhibitors had no measurable effect on cell cycle protein degradation. Therefore, hyposmotic stress inhibits cell growth and, depending on the cell type, causes cell cycle catastrophe with or without apoptosis. The growth arrest is due to decreased protein synthesis and proteasome activation, with subsequent degradation of several cyclins and Cdks.The cell cycle involves a meticulously ordered series of events that control defined cell cycle stage check points and ultimate cell division. These events are tightly regulated by the expression and degradation, activation and inactivation, and subcellular localization of cyclins and cyclin-dependent kinases (Cdks) 1 (1-3). Cyclins associate with, and activate, Cdks and are periodically synthesized then degraded during cell cycle progression, whereas cellular Cdk levels tend to remain in excess throughout the normal cell cycle (1-5). In mammalian cells, Cdk4 and Cdk6 associate with D-type cyclins and regulate G 1 cell cycle phase progression. Cdk2 associates with the Eand A-type cyclins, and the respective complexes control G 1 /S transition and S phase progression, respectively (1-5). Cdc2 (also termed Cdk1) and the B-type cyclin form a cytoplasmic complex at the G 2 /M phase checkpoint, which translocates to the nucleus just prior to nuclear envelope breakdown during prophase. Abnormal sequestering of cyclin B1/Cdc2 complexes in the cytoplasm leads to perturbation of cell cycle progression (6 -8).Most mammalian cells have developed compensatory mechanisms to respond to changes in the osmolarity of the surrounding medium, which allow them to re-establish homeostasis of osmotically disturbed aspects of cell structure and function (9, 10). These mechanisms are necessary, because osmotic stress may severely compromise eukaryotic cell function due to the importance of maintaining homeostasis of inorganic ions as a prerequisite for normal progression of metabolic processes. Disruption of such me...

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Signalling Mechanisms Involved in Volume Regulation of Intestinal Epithelial Cells

Cited by 34 publications

References 47 publications

Role of p38<sup>MAPK</sup> in Cell Volume Regulation of Perfused Rat Liver

Role of p38<sup>MAPK</sup> in Cell Volume Regulation of Perfused Rat Liver

Mechanisms Sensing and Modulating Signals Arising From Cell Swelling

Hyposmotic Stress Induces Cell Growth Arrest via Proteasome Activation and Cyclin/Cyclin-dependent Kinase Degradation

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