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Dieter Haussinger - One of the best experts on this subject based on the ideXlab platform.
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influence of Cell Volume changes on protein synthesis in isolated hepatocytes of air breathing walking catfish clarias batrachus
Fish Physiology and Biochemistry, 2010Co-Authors: Kuheli Biswas, Dieter Haussinger, Lucy M Jyrwa, Nirmalendu SahaAbstract:The present study aimed at determining the effect of Cell Volume changes on protein synthesis, measured as the incorporation of [3H]leucine into acid-precipitable protein, in isolated hepatocytes of air-breathing walking catfish (Clarias batrachus). The rate of protein synthesis, which was recorded to be 10.02 ± 0.10 (n = 25) nmoles mg−1 Cell protein h−1 in isotonic incubation conditions, increased/decreased significantly by 18 and 48%, respectively, following hypo- (−80 mOsmol l−1)/hypertonic (+80 mOsmol l−1) incubation conditions (adjusted with NaCl), with an accompanying increase/decrease of hepatic Cell Volume by 12 and 20%, respectively. Similar Cell Volume-sensitive changes of protein synthesis were also observed when the anisotonicity of incubation medium was adjusted with mannitol. Increase of hepatic Cell Volume by 9%, due to addition of glutamine plus glycine (5 mM each) to the isotonic control incubation medium, led to a significant increase of protein synthesis by 14%. Decrease of hepatic Cell Volume by 15 and 18%, due to addition of dibutyl-cAMP and adenosine in isotonic control incubation medium, led to a significant decrease of protein synthesis by 30 and 34%, respectively. Thus, it appears that the increase/decrease of hepatic Cell Volume, caused either by changing the extraCellular osmolarity or by the presence of amino acids or certain other metabolites, leads to increase/decrease of protein synthesis, respectively, and shows a direct correction (r = 0.99) between the hepatic Cell Volume and protein synthesis in walking catfish. These Cell Volume-sensitive changes of protein synthesis probably help this walking catfish in fine tuning the different metabolic pathways for better adaptation during Cell Volume changes and also to avoid the adverse affects of osmotic stress. This is the first report of Cell Volume-sensitive changes of protein synthesis in hepatic Cells of any teleosts.
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influence of Cell Volume changes on autophagic proteolysis in the perfused liver of air breathing walking catfish clarias batrachus
Journal of Experimental Zoology, 2009Co-Authors: Kuheli Biswas, Dieter Haussinger, James L Khongsngi, Nirmalendu SahaAbstract:Exposure of perfused liver of walking catfish (Clarias batrachus) to hypotonicity (80 mOsmol/L) caused swelling of liver Cells as evidenced by the increase in liver mass by 11.5%, and inhibition of ( 3 H)leucine release (as a measure of proteolysis) by 37% from the radiolabeled perfused liver. Whereas, exposure of perfused liver to hypertonicity (180 mOsmol/L) caused shrinkage of liver Cells as evidenced by the decrease in liver mass by 10.4%, and stimulation of ( 3 H)leucine release by 24%. Infusion of amino acids such as glutamine plus glycine (2 mM each) also caused increase in liver Cell Volume as evidenced by the increase in liver mass by 8.9%, and inhibition of ( 3 H)leucine release by 29%. Adjustment of anisotonicity of the media without changing the NaCl concentration in the media had almost similar effects on proteolysis in the perfused liver. A direct correlation of Cell Volume changes or hydration status of liver Cells with that of proteolysis was observed in the perfused liver regardless of whether the Cell Volume increase/decrease was evoked by anisotonic perfusion media or by the addition of amino acids. Thus, it appears that the increase/ decrease in hepatic Cell Volume could be one of the important modulators for adjusting the autophagic proteolysis in walking catfish probably to avoid the adverse affects of osmotically induced Cell Volume changes, to preserve the hepatic Cell function and for proper energy supply under osmotic stress. This is the first report of Cell Volume-sensitive changes of autophagic proteolysis in hepatic Cells of any teleosts. J. Exp. Zool. 311A:115-124, 2009. r 2008 Wiley-Liss, Inc.
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Cell Volume changes modulate cholecystokinin and carbachol stimulated amylase release in isolated rat pancreatic acini
Gastroenterology, 1997Co-Authors: Bing Han, Dieter Haussinger, Hanne Klonowskistumpe, Freimut Schliess, Kerstin Meereisschwanke, Reinhard Luthen, Naohiro Sata, C NiederauAbstract:Abstract BACKGROUND & AIMS: Changes in Cell Volume have been recently identified as modulators of Cell function and gene expression. This study evaluated the regulation of exocrine secretion by pancreatic acini on the basis of changes in Cell hydration. METHODS: Acini were exposed to hypotonicity or hypertonicity. The effects of corresponding changes in Cell Volume on various Cell functions were analyzed. RESULTS: Hypertonicity and hypotonicity caused a stepwise Cell shrinkage and swelling, respectively. Cell shrinkage decreased and Cell swelling increased amylase secretion stimulated by cholecystokinin (CCK) and carbachol but not by secretin. Changes in Cell Volume did not alter basal or CCK-stimulated calcium concentrations or CCK-stimulated inositol triphosphate generation. The regulation of secretion by Cell Volume is not mediated via changes in CCK receptor binding or protein kinase C. The increase of amylase release caused by hypotonicity was completely inhibited by cytochalasin B, colchicine, and genistein. Hypotonicity as well as CCK caused activation of mitogen-activated protein kinases. CONCLUSIONS: Changes in Cell Volume regulate exocrine secretion of pancreatic acini. The effects were found only for secretagogues that act via the calcium/inositol-trisphosphate pathway. However, the mechanisms involved are located at luminal parts of the signal-transduction cascade and involve the cytoskeleton, protein phosphorylation, and activation of mitogen-activated protein kinases. (Gastroenterology 1997 Nov;113(5):1756-66)
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ion transport in hepatocytes mechanisms and correlations to Cell Volume hormone actions and metabolism
Journal of Hepatology, 1996Co-Authors: Jurg Graf, Dieter HaussingerAbstract:IntraCellular ion homeostasis in liver Cell is accomplished through the concerted action of ion pumps, carriers and channels. Description of these elements includes the Na+/K+-ATPase, Na+/H+- and Cl-/ HCO3(-)-exchange and Na+-HCO-3(-)- and Na(+)-K(+)-2 Cl(-)-cotransport as well as K+-, Cl(-)-, Na+ and nonselective cation channels. A short section is devoted to regulation of intraCellular Ca2+ concentration. Ion flux through these elements is regulated by hormones and during experimental alterations of Cell Volume. We describe the effects of hormones and agonists on ion transport (e.g. purinergic agonists, alpha- and beta-adrenergic agonists, vasopressin, glucagon and insulin) and we emphasize the fact that altered ion transport rates may lead to Cell swelling or Cell shrinkage. Osmotically induced Cell swelling or Cell shrinkage triggers Volume regulatory responses: recovery from Cell swelling is accomplished by release of K+ and Cl- through ion channels whereas Volume gain following osmotic shrinkage involves uptake of Na+, K+ and Cl- by channels, carriers and the Na+/K+-pump. Osmotic Cell Volume changes are associated with a broad spectrum of altered Cell functions that includes changes of bile flow and bile acid transport, modulation of cytoplasmic and endosomal pH, metabolism of carbohydrate, protein and lipids, transcription and translation and alteration of cytoskeleton components (cf. Haussinger & Schliess; J. Hepatology 1995; 22: 94-100). In conclusion, we stress the concept that transduction of a hormonal signal primarily involves alteration of membrane ion transport followed by a change in Cell Volume. This change in Cell Volume appears to assist in executing a hormonal stimulus on Cell function.
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Cell Volume a second message in regulation of Cellular function
Physiology, 1995Co-Authors: Florian Lang, Gillian L Busch, Harald Volkl, Dieter HaussingerAbstract:ABSTRACT To survive, Cells must avoid excessive alterations of Cell Volume. Thus Cells have acquired a variety of strategies to main constancy of their Volume, including the modification of ion flu...
Hidenori Ichijo - One of the best experts on this subject based on the ideXlab platform.
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a novel lens for Cell Volume regulation liquid liquid phase separation
Cellular Physiology and Biochemistry, 2021Co-Authors: Shunya Ishihara, Hidenori Ichijo, Kengo WatanabeAbstract: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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Cell Volume regulation in cancer Cell migration driven by osmotic water flow
Cancer Science, 2019Co-Authors: Kazuhiro Morishita, Kengo Watanabe, Hidenori IchijoAbstract:Cancer metastasis is the most frequent cause of death for patients with cancer. The main current treatment for cancer metastasis is chemotherapy targeting cancer Cells' ability to proliferate. However, some types of cancer Cells show resistance to chemotherapy. Recently, cancer Cell migration has become the subject of interest as a novel target of cancer therapy. Cell migration requires many factors, such as the cytoskeleton, Cell-matrix adhesion and Cell Volume regulation. Here, we focus on Cell Volume regulation and the role of ion/water transport systems in Cell migration. Transport proteins, such as ion channels, ion carriers, and aquaporins, are indispensable for Cell Volume regulation under steady-state conditions and during exposure to osmotic stress. Studies from the last ~25 years have revealed that Cell Volume regulation also plays an important role in the process of Cell migration. Water flow in accordance with localized osmotic gradients generated by ion transport contributes to the driving force for Cell migration. Moreover, it has been reported that metastatic cancer Cells have higher expression of these transport proteins than nonmetastatic cancer Cells. Thus, ion/water transport proteins involved in Cell Volume regulation and Cell migration could be novel therapeutic targets for cancer metastasis. In this review, after presenting the importance of ion/water transport systems in Cell Volume regulation, we discuss the roles of transport proteins in a pathophysiological context, especially in the context of cancer Cell migration.
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a pp6 ask3 module coordinates the bidirectional Cell Volume regulation under osmotic stress
Cell Reports, 2018Co-Authors: Kengo Watanabe, Tsuyoshi Umeda, Kuniyoshi Niwa, Isao Naguro, Hidenori IchijoAbstract:Cell Volume regulation is a vital system for Cellular activities. When perturbed by hypoosmotic or hyperosmotic stress, Cells immediately induce the Cell Volume recovery system, regulatory Volume decrease (RVD) or regulatory Volume increase (RVI), respectively. In contrast to the knowledge about effector molecules, the molecular mechanisms linking osmosensing to RVD/RVI induction remain unknown. Additionally, few reciprocal responders in the bidirectional osmotic stress response have been identified. We previously reported that ASK3 bidirectionally switches its kinase activity under osmotic stress. Herein we demonstrate that ASK3 controls both RVD and RVI under osmotic stress. Using a high-content genome-wide small interfering RNA (siRNA) screen, we identify PP6 as a direct ASK3 inactivator. Furthermore, PP6 rapidly interacts with ASK3 in an osmolality-dependent manner, and it inactivates ASK3 to induce RVI and, thereby, Cell survival under hyperosmotic stress. These findings suggest that the PP6-ASK3 interaction is a core module in the bidirectional osmotic stress response.
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A PP6-ASK3 Module Coordinates the Bidirectional Cell Volume Regulation under Osmotic Stress
Elsevier, 2018Co-Authors: Kengo Watanabe, Tsuyoshi Umeda, Kuniyoshi Niwa, Isao Naguro, Hidenori IchijoAbstract:Summary: Cell Volume regulation is a vital system for Cellular activities. When perturbed by hypoosmotic or hyperosmotic stress, Cells immediately induce the Cell Volume recovery system, regulatory Volume decrease (RVD) or regulatory Volume increase (RVI), respectively. In contrast to the knowledge about effector molecules, the molecular mechanisms linking osmosensing to RVD/RVI induction remain unknown. Additionally, few reciprocal responders in the bidirectional osmotic stress response have been identified. We previously reported that ASK3 bidirectionally switches its kinase activity under osmotic stress. Herein we demonstrate that ASK3 controls both RVD and RVI under osmotic stress. Using a high-content genome-wide small interfering RNA (siRNA) screen, we identify PP6 as a direct ASK3 inactivator. Furthermore, PP6 rapidly interacts with ASK3 in an osmolality-dependent manner, and it inactivates ASK3 to induce RVI and, thereby, Cell survival under hyperosmotic stress. These findings suggest that the PP6-ASK3 interaction is a core module in the bidirectional osmotic stress response. : Osmotic stress comprises two types of information: intensity and directionality. Nevertheless, few bidirectional Cellular systems have been identified. Using a high-content genome-wide siRNA screen, Watanabe et al. unveil that a PP6-ASK3 module bidirectionally interprets and converts osmotic stress signals to control Cell Volume homeostasis. Keywords: apoptosis signal-regulating kinase 3, ASK3, protein phosphatase 6, PP6, high-content genome-wide siRNA screen, osmotic stress, Cell Volume regulatio
Kengo Watanabe - One of the best experts on this subject based on the ideXlab platform.
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a novel lens for Cell Volume regulation liquid liquid phase separation
Cellular Physiology and Biochemistry, 2021Co-Authors: Shunya Ishihara, Hidenori Ichijo, Kengo WatanabeAbstract: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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Cell Volume regulation in cancer Cell migration driven by osmotic water flow
Cancer Science, 2019Co-Authors: Kazuhiro Morishita, Kengo Watanabe, Hidenori IchijoAbstract:Cancer metastasis is the most frequent cause of death for patients with cancer. The main current treatment for cancer metastasis is chemotherapy targeting cancer Cells' ability to proliferate. However, some types of cancer Cells show resistance to chemotherapy. Recently, cancer Cell migration has become the subject of interest as a novel target of cancer therapy. Cell migration requires many factors, such as the cytoskeleton, Cell-matrix adhesion and Cell Volume regulation. Here, we focus on Cell Volume regulation and the role of ion/water transport systems in Cell migration. Transport proteins, such as ion channels, ion carriers, and aquaporins, are indispensable for Cell Volume regulation under steady-state conditions and during exposure to osmotic stress. Studies from the last ~25 years have revealed that Cell Volume regulation also plays an important role in the process of Cell migration. Water flow in accordance with localized osmotic gradients generated by ion transport contributes to the driving force for Cell migration. Moreover, it has been reported that metastatic cancer Cells have higher expression of these transport proteins than nonmetastatic cancer Cells. Thus, ion/water transport proteins involved in Cell Volume regulation and Cell migration could be novel therapeutic targets for cancer metastasis. In this review, after presenting the importance of ion/water transport systems in Cell Volume regulation, we discuss the roles of transport proteins in a pathophysiological context, especially in the context of cancer Cell migration.
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a pp6 ask3 module coordinates the bidirectional Cell Volume regulation under osmotic stress
Cell Reports, 2018Co-Authors: Kengo Watanabe, Tsuyoshi Umeda, Kuniyoshi Niwa, Isao Naguro, Hidenori IchijoAbstract:Cell Volume regulation is a vital system for Cellular activities. When perturbed by hypoosmotic or hyperosmotic stress, Cells immediately induce the Cell Volume recovery system, regulatory Volume decrease (RVD) or regulatory Volume increase (RVI), respectively. In contrast to the knowledge about effector molecules, the molecular mechanisms linking osmosensing to RVD/RVI induction remain unknown. Additionally, few reciprocal responders in the bidirectional osmotic stress response have been identified. We previously reported that ASK3 bidirectionally switches its kinase activity under osmotic stress. Herein we demonstrate that ASK3 controls both RVD and RVI under osmotic stress. Using a high-content genome-wide small interfering RNA (siRNA) screen, we identify PP6 as a direct ASK3 inactivator. Furthermore, PP6 rapidly interacts with ASK3 in an osmolality-dependent manner, and it inactivates ASK3 to induce RVI and, thereby, Cell survival under hyperosmotic stress. These findings suggest that the PP6-ASK3 interaction is a core module in the bidirectional osmotic stress response.
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A PP6-ASK3 Module Coordinates the Bidirectional Cell Volume Regulation under Osmotic Stress
Elsevier, 2018Co-Authors: Kengo Watanabe, Tsuyoshi Umeda, Kuniyoshi Niwa, Isao Naguro, Hidenori IchijoAbstract:Summary: Cell Volume regulation is a vital system for Cellular activities. When perturbed by hypoosmotic or hyperosmotic stress, Cells immediately induce the Cell Volume recovery system, regulatory Volume decrease (RVD) or regulatory Volume increase (RVI), respectively. In contrast to the knowledge about effector molecules, the molecular mechanisms linking osmosensing to RVD/RVI induction remain unknown. Additionally, few reciprocal responders in the bidirectional osmotic stress response have been identified. We previously reported that ASK3 bidirectionally switches its kinase activity under osmotic stress. Herein we demonstrate that ASK3 controls both RVD and RVI under osmotic stress. Using a high-content genome-wide small interfering RNA (siRNA) screen, we identify PP6 as a direct ASK3 inactivator. Furthermore, PP6 rapidly interacts with ASK3 in an osmolality-dependent manner, and it inactivates ASK3 to induce RVI and, thereby, Cell survival under hyperosmotic stress. These findings suggest that the PP6-ASK3 interaction is a core module in the bidirectional osmotic stress response. : Osmotic stress comprises two types of information: intensity and directionality. Nevertheless, few bidirectional Cellular systems have been identified. Using a high-content genome-wide siRNA screen, Watanabe et al. unveil that a PP6-ASK3 module bidirectionally interprets and converts osmotic stress signals to control Cell Volume homeostasis. Keywords: apoptosis signal-regulating kinase 3, ASK3, protein phosphatase 6, PP6, high-content genome-wide siRNA screen, osmotic stress, Cell Volume regulatio
Erich Gulbins - One of the best experts on this subject based on the ideXlab platform.
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Cell Volume regulatory ion channels in Cell proliferation and Cell death
Methods in Enzymology, 2007Co-Authors: Florian Lang, Markus Ritter, Ildikò Szabò, Stephan M. Huber, Philipp A Lang, Michael Foller, Karl A Lang, A A Vereninov, Erich GulbinsAbstract:Abstract Alterations of Cell Volume are key events during both Cell proliferation and apoptotic Cell death. Cell proliferation eventually requires an increase of Cell Volume, and apoptosis is typically paralleled by Cell shrinkage. Alterations of Cell Volume require the participation of ion transport across the Cell membrane, including appropriate activity of Cl − and K + channels. Cl − channels modify cytosolic Cl − activity and mediate osmolyte flux, and thus influence Cell Volume. Most Cl − channels allow exit of HCO 3 − , leading to cytosolic acidification, which in turn inhibits Cell proliferation and favors apoptosis. K + exit through K + channels decreases cytosolic K + concentration, which may sensitize the Cell for apoptotic Cell death. K + channel activity further maintains the Cell membrane potential, a critical determinant of Ca 2+ entry through Ca 2+ channels. Ca 2+ may, in addition, enter through Ca 2+ ‐permeable cation channels, which, in some Cells, are activated by hyperosmotic shock. Increases of cytosolic Ca 2+ activity may trigger both mechanisms required for Cell proliferation and mechanisms, leading to apoptosis. Thereby Cell proliferation and apoptosis depend on magnitude and temporal organization of Ca 2+ entry, as well as activity of other signaling pathways. Accordingly, the same ion channels may participate in the stimulation of both Cell proliferation and apoptosis. Specific ion channel blockers may thus abrogate both Cellular mechanisms, depending on Cell type and condition.
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Cell Volume and the regulation of apoptotic Cell death
Journal of Molecular Recognition, 2004Co-Authors: Florian Lang, Ildikò Szabò, Stephan M. Huber, Erich Gulbins, Albrecht Lepplewienhues, Christophe Duranton, Karl S Lang, Philipp A Lang, Thomas WiederAbstract:Apoptosis is a physiological mechanism allowing for the removal of abundant or potentially harmful Cells. The hallmarks of apoptosis include degradation of Cellular DNA, exposure of phosphatidylserine at the outer leaflet of the Cell membrane and Cell shrinkage. Phosphatidylserine exposure favours adhesion to macrophages with subsequent phagocytosis of the shrunken apoptotic particles. The interaction of Cell Volume regulatory mechanisms and apoptosis is illustrated in two different model systems, i.e. (a) lymphocyte apoptosis following stimulation of CD95 receptor and (b) erythrocyte apoptosis upon Cell shrinkage. (a) Triggering of CD95 in Jurkat T lymphocytes is paralleled by activation of Cell Volume regulatory Cl- channels, inhibition of the Na+/H+ exchanger and osmolyte release. The latter coincides with Cell shrinkage, DNA fragmentation and phosphatidylserine exposure. CD95 stimulation leads to early inhibition of the voltage gated K+ channel Kv1.3, which may contribute to the inhibition of the Ca2+ release activated Ca2+ channel I(CRAC). (b) Osmotic shock of erythrocytes activates a Cell Volume regulatory cation conductance allowing the entry not only of Na+ but of Ca2+ as well. Increased cytosolic Ca2+ stimulates a scramblase which disrupts the phosphatidylserine asymmetry of the Cell membrane, leading to phosphatidylserine exposure. The cation conductance is further activated by oxidative stress and energy depletion and inhibited by Cl-. Shrinkage of erythrocytes stimulates in addition a sphingomyelinase with subsequent formation of ceramide which potentiates the effect of cytosolic Ca2+ on phosphatidylserine. In conclusion, Cell Volume-sensitive mechanisms participate in the triggering of apoptosis following receptor stimulation or Cell injury.
Florian Lang - One of the best experts on this subject based on the ideXlab platform.
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Cell Volume regulatory ion channels in Cell proliferation and Cell death
Methods in Enzymology, 2007Co-Authors: Florian Lang, Markus Ritter, Ildikò Szabò, Stephan M. Huber, Philipp A Lang, Michael Foller, Karl A Lang, A A Vereninov, Erich GulbinsAbstract:Abstract Alterations of Cell Volume are key events during both Cell proliferation and apoptotic Cell death. Cell proliferation eventually requires an increase of Cell Volume, and apoptosis is typically paralleled by Cell shrinkage. Alterations of Cell Volume require the participation of ion transport across the Cell membrane, including appropriate activity of Cl − and K + channels. Cl − channels modify cytosolic Cl − activity and mediate osmolyte flux, and thus influence Cell Volume. Most Cl − channels allow exit of HCO 3 − , leading to cytosolic acidification, which in turn inhibits Cell proliferation and favors apoptosis. K + exit through K + channels decreases cytosolic K + concentration, which may sensitize the Cell for apoptotic Cell death. K + channel activity further maintains the Cell membrane potential, a critical determinant of Ca 2+ entry through Ca 2+ channels. Ca 2+ may, in addition, enter through Ca 2+ ‐permeable cation channels, which, in some Cells, are activated by hyperosmotic shock. Increases of cytosolic Ca 2+ activity may trigger both mechanisms required for Cell proliferation and mechanisms, leading to apoptosis. Thereby Cell proliferation and apoptosis depend on magnitude and temporal organization of Ca 2+ entry, as well as activity of other signaling pathways. Accordingly, the same ion channels may participate in the stimulation of both Cell proliferation and apoptosis. Specific ion channel blockers may thus abrogate both Cellular mechanisms, depending on Cell type and condition.
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mechanisms and significance of Cell Volume regulation
Journal of The American College of Nutrition, 2006Co-Authors: Florian LangAbstract:Survival of human and animal Cells requires avoidance of excessive alterations of Cell Volume. The osmolarity amassed by Cellular accumulation of organic substances must be compensated by lowering cytosolic ion concentrations. The Na+/K+ ATPase extrudes Na+ in exchange for K+, which can permeate the Cell membrane through K+ channels. K+ exit generates a Cell-negative potential difference across the Cell membrane, driving the exit of anions such as Cl−. The low cytosolic Cl− concentrations counterbalance the excess Cellular osmolarity by organic substances. Cell Volume regulation following Cell swelling involves releasing ions through activation of K+ channels and/or anion channels, KCl-cotransport, or parallel activation of K+/H+ exchange and Cl−/HCO3− exchange. Cell Volume regulation following Cell shrinkage involves accumulation of ions through activation of Na+,K+,2Cl− cotransport, Na+/H+ exchange in parallel to Cl−/HCO3− exchange, or Na+ channels. The Na+ taken up is extruded by the Na+/K+ ATPase in e...
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mechanisms and significance of Cell Volume regulation
Published in 2006 in Basel by S Karger, 2006Co-Authors: Florian LangAbstract:It is essential for the survival of Cells to maintain their Volume within certain limits: Profound alterations interfere with the integrity of the Cell membrane and the cytoskeletal architecture. Cells use various methods to adjust osmotic pressure gradients which in turn govern water movement across Cell membranes. The most rapid and efficient means is ion transport across the Cell membrane. However, to avoid excessive alterations of intraCellular ion concentration, Cells additionally employ organic osmolytes for osmoregulation and modify their metabolism, thus generating or disposing osmotically active organic substances. But a given Cell uses only part of the Cell Volume regulatory mechanisms at their disposal: The large repertoire available allows for a selection of those which have the least untoward impact on Cell function.The present book is a collection of reviews on the various aspects of Cell Volume regulation, written by internationally leading experts, and constitutes a valuable addition to the library of those working in the field.
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Cell Volume and the regulation of apoptotic Cell death
Journal of Molecular Recognition, 2004Co-Authors: Florian Lang, Ildikò Szabò, Stephan M. Huber, Erich Gulbins, Albrecht Lepplewienhues, Christophe Duranton, Karl S Lang, Philipp A Lang, Thomas WiederAbstract:Apoptosis is a physiological mechanism allowing for the removal of abundant or potentially harmful Cells. The hallmarks of apoptosis include degradation of Cellular DNA, exposure of phosphatidylserine at the outer leaflet of the Cell membrane and Cell shrinkage. Phosphatidylserine exposure favours adhesion to macrophages with subsequent phagocytosis of the shrunken apoptotic particles. The interaction of Cell Volume regulatory mechanisms and apoptosis is illustrated in two different model systems, i.e. (a) lymphocyte apoptosis following stimulation of CD95 receptor and (b) erythrocyte apoptosis upon Cell shrinkage. (a) Triggering of CD95 in Jurkat T lymphocytes is paralleled by activation of Cell Volume regulatory Cl- channels, inhibition of the Na+/H+ exchanger and osmolyte release. The latter coincides with Cell shrinkage, DNA fragmentation and phosphatidylserine exposure. CD95 stimulation leads to early inhibition of the voltage gated K+ channel Kv1.3, which may contribute to the inhibition of the Ca2+ release activated Ca2+ channel I(CRAC). (b) Osmotic shock of erythrocytes activates a Cell Volume regulatory cation conductance allowing the entry not only of Na+ but of Ca2+ as well. Increased cytosolic Ca2+ stimulates a scramblase which disrupts the phosphatidylserine asymmetry of the Cell membrane, leading to phosphatidylserine exposure. The cation conductance is further activated by oxidative stress and energy depletion and inhibited by Cl-. Shrinkage of erythrocytes stimulates in addition a sphingomyelinase with subsequent formation of ceramide which potentiates the effect of cytosolic Ca2+ on phosphatidylserine. In conclusion, Cell Volume-sensitive mechanisms participate in the triggering of apoptosis following receptor stimulation or Cell injury.
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Cell Volume a second message in regulation of Cellular function
Physiology, 1995Co-Authors: Florian Lang, Gillian L Busch, Harald Volkl, Dieter HaussingerAbstract:ABSTRACT To survive, Cells must avoid excessive alterations of Cell Volume. Thus Cells have acquired a variety of strategies to main constancy of their Volume, including the modification of ion flu...