Levels of Organic Osmolytes in Normal and Diuretic Rat Kidneys1

2015 ◽  
pp. 279-283 ◽  
Author(s):  
K. H. Lee ◽  
S. B. Lee ◽  
K. C. Cho
Keyword(s):  
Organic Osmolytes

More than just a pressure relief valve: physiological roles of volume-regulated LRRC8 anion channels

2019 ◽  
Vol 400 (11) ◽  
pp. 1481-1496 ◽  
Author(s):  
Lingye Chen ◽  
Benjamin König ◽  
Tianbao Liu ◽  
Sumaira Pervaiz ◽  
Yasmin S. Razzaque ◽  
...  
Keyword(s):  
Volume Regulation ◽  
Regulatory Volume Decrease ◽  
Anion Channel ◽  
Therapy Resistance ◽  
Cell Swelling ◽  
Organic Osmolytes ◽  
Anion Channels ◽  
Relief Valve ◽  
Wide Range ◽  
And Migration

Abstract The volume-regulated anion channel (VRAC) is a key player in the volume regulation of vertebrate cells. This ubiquitously expressed channel opens upon osmotic cell swelling and potentially other cues and releases chloride and organic osmolytes, which contributes to regulatory volume decrease (RVD). A plethora of studies have proposed a wide range of physiological roles for VRAC beyond volume regulation including cell proliferation, differentiation and migration, apoptosis, intercellular communication by direct release of signaling molecules and by supporting the exocytosis of insulin. VRAC was additionally implicated in pathological states such as cancer therapy resistance and excitotoxicity under ischemic conditions. Following extensive investigations, 5 years ago leucine-rich repeat-containing family 8 (LRRC8) heteromers containing LRRC8A were identified as the pore-forming components of VRAC. Since then, molecular biological approaches have allowed further insight into the biophysical properties and structure of VRAC. Heterologous expression, siRNA-mediated downregulation and genome editing in cells, as well as the use of animal models have enabled the assessment of the proposed physiological roles, together with the identification of new functions including spermatogenesis and the uptake of antibiotics and platinum-based cancer drugs. This review discusses the recent molecular biological insights into the physiology of VRAC in relation to its previously proposed roles.

Transcriptional targets of DAF-16 insulin signaling pathway protect C. elegans from extreme hypertonic stress

2005 ◽  
Vol 288 (2) ◽  
pp. C467-C474 ◽  
Author(s):  
S. Todd Lamitina ◽  
Kevin Strange
Keyword(s):  
Insulin Signaling ◽  
Stress Resistance ◽  
Molecular Mechanisms ◽  
Organic Osmolytes ◽  
Dependent Manner ◽  
Animal Cells ◽  
Hypertonic Stress ◽  
C Elegans ◽  
Downstream Target ◽  
Molecular Damage

All cells adapt to hypertonic stress by regulating their volume after shrinkage, by accumulating organic osmolytes, and by activating mechanisms that protect against and repair hypertonicity-induced damage. In mammals and nematodes, inhibition of signaling from the DAF-2/IGF-1 insulin receptor activates the DAF-16/FOXO transcription factor, resulting in increased life span and resistance to some types of stress. We tested the hypothesis that inhibition of insulin signaling in Caenorhabditis elegans also increases hypertonic stress resistance. Genetic inhibition of DAF-2 or its downstream target, the AGE-1 phosphatidylinositol 3-kinase, confers striking resistance to a normally lethal hypertonic shock in a DAF-16-dependent manner. However, insulin signaling is not inhibited by or required for adaptation to hypertonic conditions. Microarray studies have identified 263 genes that are transcriptionally upregulated by DAF-16 activation. We identified 14 DAF-16-upregulated genes by RNA interference screening that are required for age- 1 hypertonic stress resistance. These genes encode heat shock proteins, proteins of unknown function, and trehalose synthesis enzymes. Trehalose levels were elevated approximately twofold in age- 1 mutants, but this increase was insufficient to prevent rapid hypertonic shrinkage. However, age- 1 animals unable to synthesize trehalose survive poorly under hypertonic conditions. We conclude that increased expression of proteins that protect eukaryotic cells against environmental stress and/or repair stress-induced molecular damage confers hypertonic stress resistance in C. elegans daf- 2/ age- 1 mutants. Elevated levels of solutes such as trehalose may also function in a cytoprotective manner. Our studies provide novel insights into stress resistance in animal cells and a foundation for new studies aimed at defining molecular mechanisms underlying these essential processes.

scholarly journals Simultaneous Biochemical and Physiological Responses of the Roots and Leaves of Pancratium maritimum (Amaryllidaceae) to Mild Salt Stress

Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 345
Author(s):  
Simona Carfagna ◽  
Giovanna Salbitani ◽  
Michele Innangi ◽  
Bruno Menale ◽  
Olga De Castro ◽  
...  
Keyword(s):  
Salt Stress ◽  
Reduced Glutathione ◽  
Physiological Responses ◽  
Leaf Tissue ◽  
Electron Donors ◽  
Organic Osmolytes ◽  
Glutathione Disulfide ◽  
Stress Changes ◽  
Leaves And Roots ◽  
Pancratium Maritimum

Pancratium maritimum (Amaryllidaceae) is a bulbous geophyte growing on coastal sands. In this study, we investigated changes in concentrations of metabolites in the root and leaf tissue of P. maritimum in response to mild salt stress. Changes in concentrations of osmolytes, glutathione, sodium, mineral nutrients, enzymes, and other compounds in the leaves and roots were measured at 0, 3, and 10 days during a 10-day exposure to two levels of mild salt stress, 50 mM NaCl or 100 mM NaCl in sandy soil from where the plants were collected in dunes near Cuma, Italy. Sodium accumulated in the roots, and relatively little was translocated to the leaves. At both concentrations of NaCl, higher values of the concentrations of oxidized glutathione disulfide (GSSG), compared to reduced glutathione (GSH), in roots and leaves were associated with salt tolerance. The concentration of proline increased more in the leaves than in the roots, and glycine betaine increased in both roots and leaves. Differences in the accumulation of organic osmolytes and electron donors synthesized in both leaves and roots demonstrate that osmoregulatory and electrical responses occur in these organs of P. maritimum under mild salt stress.

CD9 antigen mRNA is induced by hypertonicity in two renal epithelial cell lines

1996 ◽  
Vol 270 (1) ◽  
pp. C253-C258 ◽  
Author(s):  
D. Sheikh-Hamad ◽  
J. D. Ferraris ◽  
J. Dragolovich ◽  
H. G. Preuss ◽  
M. B. Burg ◽  
...  
Keyword(s):  
Stress Response ◽  
Cell Lines ◽  
Gene Transcription ◽  
Hyperosmotic Stress ◽  
Surface Glycoprotein ◽  
Specific Gene ◽  
Organic Osmolytes ◽  
Cell Surface Glycoprotein ◽  
Hypertonic Medium ◽  
Mrna Induction

In diverse organisms, cells adapt to hyperosmotic stress by accumulating organic osmolytes. Mammalian renal medullary cells are routinely under osmotic stress. Two renal cell lines, Madin-Darby canine kidney (MDCK) and PAP-HT25, have been widely used to study mammalian osmotic regulation. In these epithelial cells, extracellular hypertonicity induces gene transcription of proteins directly involved in the metabolism and transport of organic osmolytes. This induction is relatively specific and not part of a generalized stress response. Little is known about the signal transduction pathway between cellular detection of extracellular osmolality and increased specific gene transcription. Here, using differential mRNA display polymerase chain reaction on MDCK cells in isotonic vs. hypertonic medium, we identify a cDNA product corresponding to CD9 antigen mRNA. CD9 antigen is a cell surface glycoprotein originally found in cells of the immune system. Although CD9 antigen has been structurally characterized, its function is unclear. We further demonstrate that CD9 antigen mRNA is present in MDCK and PAP-HT25 cells and that its mRNA abundance is induced by extracellular hypertonicity, but not by heat stress. Also, we show that accumulation of organic osmolytes markedly attenuates the CD9 mRNA induction, as only recently demonstrated with genes involved in the hyperosmotic stress response. This suggests a role for CD9 antigen in this response.

Nutritional and physiological responses of the dicotyledonous halophyte Sarcocornia fruticosa to salinity

2017 ◽  
Vol 65 (7) ◽  
pp. 573 ◽  
Author(s):  
Pedro García-Caparrós ◽  
Alfonso Llanderal ◽  
Maribela Pestana ◽  
Pedro José Correia ◽  
María Teresa Lao
Keyword(s):  
Dry Weight ◽  
Biofuel Production ◽  
Peat Moss ◽  
Organic Osmolytes ◽  
Salinity Treatment ◽  
Tissue Water ◽  
Plant Parts ◽  
Sphagnum Peat Moss ◽  
Net Uptake ◽  
Sarcocornia Fruticosa

Sarcocornia fruticosa (L.) A.J. Scott is a dicotyledonous halophyte that grows in areas with an arid climate such as the marshes of southern Spain. The species has potential uses for saline agriculture and biofuel production, but the effects of salt stress on its nutrition and physiology remain unclear. Plants of S. fruticosa were grown in pots with a mixture of sphagnum peat-moss and Perlite. In order to evaluate the effects of different levels of salinity, five treatments using different NaCl concentrations (10 (control), 60, 100, 200 and 300 mM NaCl) were applied over a period of 60 days. At the end of the experiment, the dry weight, the biomass allocation and the tissue water content were measured for each salinity treatment. The net uptake of various nutrients and their translocation rates were calculated for each salt treatment. Salt loss, shedding of plant parts and succulence in shoots were evaluated together with the K+/Na+ ratio, K-Na selectivity, concentrations of osmolytes and their estimated contributions to the osmotic potential. Our results showed that S. fruticosa can maintain its major physiological processes at 60 mM NaCl without significant dry weight reduction. Higher salinity resulted in negative values for net uptake and translocation rates from roots to shoots of N and P. As might be predicted from other dicotyledonous halophytes, S. fruticosa plants increased Cl– and Na+ uptake using both as osmotica instead of organic osmolytes. However, to survive salinity, this species has also evolved others mechanisms such as shedding old shoots, increased succulence in shoots at higher salt concentrations and the ability to maintain a lower K+/Na+ ratio and higher K-Na selectivity in all organs.

The volume-sensitive organic osmolyte-anion channel VSOAC is regulated by nonhydrolytic ATP binding

1994 ◽  
Vol 267 (5) ◽  
pp. C1203-C1209 ◽  
Author(s):  
P. S. Jackson ◽  
R. Morrison ◽  
K. Strange
Keyword(s):  
Ketone Bodies ◽  
Anion Channel ◽  
Metabolic Inhibitors ◽  
Cell Swelling ◽  
Organic Osmolytes ◽  
Pipette Solution ◽  
Organic Osmolyte ◽  
Atp Levels ◽  
Patch Pipette ◽  
Taurine Efflux

Efflux of intracellular organic osmolytes to the external medium is a ubiquitous response to cell swelling. Accumulating evidence indicates that volume regulatory loss of structurally unrelated organic osmolytes from cells is mediated by a relatively nonselective volume-sensitive anion channel. In C6 cells, we have termed this channel VSOAC for volume-sensitive organic osmolyte-anion channel. Swelling-induced activation of VSOAC required the presence of ATP or nonhydrolyzable ATP analogues [adenosine 5'-O-(3-thiotriphosphate), adenylylmethyl-enediphosphonate (AMP-PCP), or 5'-adenylylimidodiphosphate] in the patch pipette. Sustained activation of VSOAC also required ATP. Channel rundown was observed when cellular ATP levels were lowered by intracellular dialysis with the patch pipette solution. Rundown was prevented by the ATP analogue AMP-PCP. Passive swelling-induced myo-[3H]inositol and [3H]taurine efflux was blocked by metabolic inhibitors that decreased cellular ATP levels. Titration of cellular ATP levels with azide demonstrated that the apparent dissociation constant (Kd) for ATP of both myo-inositol and taurine efflux was approximately 1.7 mM. The high Kd for ATP indicates that cellular metabolic state plays an important role in modulating organic osmolyte loss. Regulation of VSOAC activity by ATP prevents depletion of metabolically expensive organic osmolytes when cellular energy production is reduced. In addition, ATP-dependent regulation provides essential feedback to minimize the loss of energy-producing carbon sources such as pyruvate, short-chain fatty acids, ketone bodies, and amino acids, which readily permeate this channel.

scholarly journals A Novel Lens for Cell Volume Regulation: Liquid-Liquid Phase Separation

2021 ◽  
Vol 55 (S1) ◽  
pp. 135-160
Keyword(s):  
Phase Separation ◽  
Cell Membrane ◽  
Cell Volume ◽  
Volume Change ◽  
Cell Biology ◽  
Cell Volume Regulation ◽  
Organic Osmolytes ◽  
Regulatory Systems ◽  
Osmotic Water ◽  
Intracellular Changes

Cells are constantly exposed to the risk of volume perturbation under physiological conditions. The increase or decrease in cell volume accompanies intracellular changes in cell membrane tension, ionic strength/concentration and macromolecular crowding. To avoid deleterious consequences caused by cell volume perturbation, cells have volume recovery systems that regulate osmotic water flow by transporting ions and organic osmolytes across the cell membrane. Thus far, a number of biomolecules have been reported to regulate cell volume. However, the question of how cells sense volume change and modulate volume regulatory systems is not fully understood. Recently, the existence and significance of phaseseparated biomolecular condensates have been revealed in numerous physiological events, including cell volume perturbation. In this review, we summarize the current understanding of cell volume-sensing mechanisms, introduce recent studies on biomolecular condensates induced by cell volume change and discuss how biomolecular condensates contribute to cell volume sensing and cell volume maintenance. In addition to previous studies of biochemistry, molecular biology and cell biology, a phase separation perspective will allow us to understand the complicated volume regulatory systems of cells.

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