Cell volume homeostatic mechanisms: effectors and signalling pathways

Hoffmann, Else K.; Pedersen, Stine Falsig

doi:10.1111/j.1748-1716.2010.02190.x

Cited by 76 publications

(62 citation statements)

References 230 publications

(286 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…18 After OP, RVD phase occurs and is completed within 30 min of hyposmotic shock application, with cell volume recovering, due to both K + and Cl -outflow, resulting in water efflux. 18,30 Here we demonstrate that time exposure comprised between 30 min and overnight did not induce cell death under either 1 or 10 or 100 µM Cd 2+ . Furthermore, both 1 and 10 µM Cd 2+ -treated HEK 293 cells did not exhibit a peak value comparable to that observed in untreated cells.…”

Section: Discussionmentioning

confidence: 91%

“…[27][28][29] On this basis, cultured human embryonic kidney (HEK 293 Phoenix) cells have been chosen as a model to define whether heavy metals like Cd 2+ , deriving from environmental pollution, 4 may affect cell volume regulation under hyposmotic shock, a homeostatic parameter recognized to be essential for survival of many cells. 13,30 Being renal cells continuously exposed to physiological changes in the osmolarity of the external medium, 31 cell lines derived from kidney are a suitable model for monitoring homeostatic cell functions, such as the regulation of cellular volume, in the presence of xenobiotics. 32,33 Our results show that HEK 293 cells exhibit the expected OP within 4 min of 15% hyposmotic challenge, leading to water influx, as shown in other cell types.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cadmium affects osmotic phase and regulatory volume decrease in cultured human embryonic kidney cells

et al. 2016

View full text Add to dashboard Cite

The present investigation aims to verify whether cadmium (Cd 2+ ), a metal possibly accumulated in body tissues from air and food, affects cell volume regulation capability in cultured human embryonic kidney (HEK 293 Phoenix) cells. The osmotic phase (OP), which is the expected cell swelling due to aquaporins involvement after hyposmotic challenge, and regulatory volume decrease (RVD), bringing cell volume back to control values through Ca 2+ -dependent ion efflux (K + and Cl -), have been monitored in HEK 293 cells treated with Cd 2+ (1-10-100 µM) for different time intervals (30 min, 3 h, overnight) and then submitted to 15 % hyposmotic shock. The results show that both 1 and 10 µM Cd 2+ significantly reduced OP, whereas 100 µM impaired Cd 2+ RVD mechanisms. The use of glutathione (GSH, 200 µM) confirmed that Cd 2+ elicited its effect via oxidative damage, being RVD inhibition after Cd 2+ treatment prevented by this antioxidant compound. Our findings show that: i) HEK 293 cells are a suitable model to assay the effect of xenobiotics on cell homeostasis; ii) Cd 2+ , depending on its concentration, affects cell homeostasis at different levels, i.e. water and ion permeability, responsible for, respectively, OP and RVD mechanism, adding thus more information to the knowledge of Cd 2+ toxicology.

show abstract

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Cadmium affects osmotic phase and regulatory volume decrease in cultured human embryonic kidney cells

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The P2 blockers cibacron blue and suramin were reported to inhibit volume sensitive Cl Ϫ channels (28,29), so that the observed inhibition of RVD by both P2 blockers might be due to inhibition of Cl Ϫ permeability. Accordingly, incubation of Huh-7 in hypotonic medium with the chloride channel blocker glibenclamide (400 M) inhibited RVD to a similar extent than medium H ϩ Cb ϩ S (RVD 40 ϭ 17.5 Ϯ 2.53 and 11.9 Ϯ 3.17%, respectively; Fig.…”

Section: Effects Of Glibenclamide On Rvdmentioning

confidence: 99%

“…Swollen cells of liver and hepatoma cells lose Cl Ϫ and K ϩ through electroneutral ion transport pathways or by the separate activation of K ϩ and anion channels (27). Although many intracellular signaling processes of cell volume regulation are now well characterized (29), comparatively little is known regarding the extracellular factors controlling RVD (14,48,49). In this respect, mechanical stimuli such as shear stress (7), mechanical strain (55), and hypotonic stress (45) have been shown to induce the release of ATP in the absence of lysis from a variety of cells (36,44,51,52,61), whereas addition of exogenous ATP to hypotonic cells suspensions was able to stimulate RVD (32,49).…”

mentioning

confidence: 99%

On the role of ATP release, ectoATPase activity, and extracellular ADP in the regulatory volume decrease of Huh-7 human hepatoma cells

Espelt

Pinto

Álvarez

et al. 2013

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

Espelt MV, de Tezanos Pinto F, Alvarez CL, Alberti GS, Incicco J, Denis MF, Davio C, Schwarzbaum PJ. On the role of ATP release, ectoATPase activity, and extracellular ADP in the regulatory volume decrease of Huh-7 human hepatoma cells. Am J Physiol Cell Physiol 304: C1013-C1026, 2013. First published March 13, 2013 doi:10.1152/ajpcell.00254.2012.-Hypotonicity triggered in human hepatoma cells (Huh-7) the release of ATP and cell swelling, followed by volume regulatory decrease (RVD). We analyzed how the interaction between those processes modulates cell volume. Cells exposed to hypotonic medium swelled 1.5 times their basal volume. Swelling was followed by 41% RVD 40 (extent of RVD after 40 min of maximum), whereas the concentration of extracellular ATP (ATP e) increased 10 times to a maximum value at 15 min. Exogenous apyrase (which removes di-and trinucleotides) did not alter RVD, whereas exogenous Na ϩ -K ϩ -ATPase (which converts ATP to ADP in the extracellular medium) enhanced RVD 40 by 2.6 times, suggesting that hypotonic treatment alone produced a basal RVD, whereas extracellular ADP activated RVD to achieve complete volume regulation (i.e., RVD40 Ϸ100%). Under hypotonicity, addition of 2-(methylthio)adenosine 5=-diphosphate (2MetSADP; ADP analog) increased RVD to the same extent as exposure to Na ϩ -K ϩ -ATPase and the same analog did not stimulate RVD when coincubated with MRS2211, a blocker of ADP receptor P2Y 13. RT-PCR and Western blot analysis confirmed the presence of P2Y 13. Cells exhibited significant ectoATPase activity, which according to RT-PCR analysis can be assigned to ENTPDase2. Both carbenoxolone, a blocker of conductive ATP release, and brefeldin A, an inhibitor of exocytosis, were able to partially decrease ATP e accumulation, pointing to the presence of at least two mechanisms for ATP release. Thus, in Huh-7 cells, hypotonic treatment triggered the release of ATP. Conversion of ATP e to ADPe by ENTPDase 2 activity facilitates the accumulated ADP e to activate P2Y13 receptors, which mediate complete RVD.cell volume regulation; human hepatoma; nucleotides; P2Y13 receptor; purinergic signaling IN MOST ANIMAL CELLS, A REDUCTION of extracellular osmolarity or an increase in intracellular osmolarity leads to a net influx of water causing volume increase. Not surprisingly, cells exhibit volume regulatory mechanisms that prevent excessive swelling leading to cell bursting and excessive shrinkage that would compromise proper cell metabolism (24). Cell swelling is followed by a slower recovery towards the preshock level, a process known as regulatory volume decrease (RVD; Refs. 27,38). This response is mediated to a large extent by the efflux of intracellular osmolytes, thereby generating a driving force for water efflux. Swollen cells of liver and hepatoma cells lose Cl Ϫ and K ϩ through electroneutral ion transport pathways or by the separate activation of K ϩ and anion channels (27). Although many intracellular signaling processes of cell volume regulation are now well characterized (29), c...

show abstract

“…Perturbations in cell volume evoke wide-ranging signaling events leading to acute protective responses (e.g., rearrangement of the cytoskeleton) and longer-term adaptive responses (e.g., alterations in osmolyte transport and gene expression) (1). During acute swelling, cells can respond by a process of regulatory cell volume decrease (RVD).…”

mentioning

confidence: 99%

Evidence for Extracellular ATP as a Stress Signal in a Single-Celled Organism

Sivaramakrishnan

Fountain

2015

Eukaryot Cell

View full text Add to dashboard Cite

ATP is omnipresent in biology and acts as an extracellular signaling molecule in mammals. Information regarding the signaling function of extracellular ATP in single-celled eukaryotes is lacking. Here, we explore the role of extracellular ATP in cell volume recovery during osmotic swelling in the amoeba Dictyostelium. Release of micromolar ATP could be detected during cell swelling and regulatory cell volume decrease (RVD) phases during hypotonic challenge. Scavenging ATP with apyrase caused profound cell swelling and loss of RVD. Apyrase-induced swelling could be rescued by 100 M ␤␥-imidoATP. N-Ethylmalemide (NEM), an inhibitor of vesicular exocytosis, caused heightened cell swelling, loss of RVD, and inhibition of ATP release. Amoebas with impaired contractile vacuole (CV) fusion (drainin knockout [KO] cells) displayed increased swelling but intact ATP release. One hundred micromolar Gd 3؉ caused cell swelling while blocking any recovery by ␤␥-imidoATP. ATP release was 4-fold higher in the presence of Gd 3؉ . Cell swelling was associated with an increase in intracellular nitric oxide (NO), with NO-scavenging agents causing cell swelling. Swelling-induced NO production was inhibited by both apyrase and Gd 3؉ , while NO donors rescued apyrase-and Gd 3؉ -induced swelling. These data suggest extracellular ATP released during cell swelling is an important signal that elicits RVD. Though the cell surface receptor for ATP in Dictyostelium remains elusive, we suggest ATP operates through a Gd 3؉ -sensitive receptor that is coupled with intracellular NO production.T he ability to control cell volume is an essential function for cell survival in the face of osmotic challenge. Perturbations in cell volume evoke wide-ranging signaling events leading to acute protective responses (e.g., rearrangement of the cytoskeleton) and longer-term adaptive responses (e.g., alterations in osmolyte transport and gene expression) (1). During acute swelling, cells can respond by a process of regulatory cell volume decrease (RVD). Under normal physiological conditions, mammalian cells are exposed to extracellular fluid osmolarity of approximately 285 mosmol, which is kept constant by normal body fluid homeostasis. Cell swelling often occurs as a consequence of changes to the intracellular composition of osmolytes, which results in intracellular hypotonicity and the influx of water. Compositional changes may occur during increased cellular transport or accumulation of nutrients or metabolic waste. Osmotically swollen mammalian cells release K ϩ , Cl Ϫ , and nonessential organic osmolytes in an effort to reverse the flow of water by osmosis. In contrast to mammalian cells, free-living single eukaryotic cells can be subjected to rapid and harsh changes in the osmolarity of the extracellular environment. As a consequence, the majority of single-celled organisms have evolved a specialized organelle called the contractile vacuole, a bladder-like structure that plays a major role in extruding water from the cytoplasm and expelling it into the ex...

show abstract

Cell volume homeostatic mechanisms: effectors and signalling pathways

Cited by 76 publications

References 230 publications

Cadmium affects osmotic phase and regulatory volume decrease in cultured human embryonic kidney cells

Cadmium affects osmotic phase and regulatory volume decrease in cultured human embryonic kidney cells

On the role of ATP release, ectoATPase activity, and extracellular ADP in the regulatory volume decrease of Huh-7 human hepatoma cells

Evidence for Extracellular ATP as a Stress Signal in a Single-Celled Organism

Contact Info

Product

Resources

About