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Joseph G Verbalis - One of the best experts on this subject based on the ideXlab platform.
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Disorders of water metabolism: diabetes insipidus and the syndrome of inappropriate antidiuretic hormone secretion
Handbook of clinical neurology, 2014Co-Authors: Joseph G VerbalisAbstract:Disorders of body fluids are among the most commonly encountered problems in the practice of clinical medicine. This is in large part because many different disease states can potentially disrupt the finely balanced mechanisms that control the intake and output of water and solute. It therefore behooves clinicians treating such patients to have a good understanding of the pathophysiology, the differential diagnosis and the management of these disorders. Since body water is the primary determinant of the osmolality of the extracellular fluid (ECF), disorders of body water homeostasis can be divided into hypoosmolar disorders, in which there is an excess of body water relative to body solute, and hyperosmolar disorders, in which there is a deficiency of body water relative to body solute. The classical hyperosmolar disorder is diabetes insipidus (DI), and the classical hypoosmolar disorder is the syndrome of inappropriate antidiuretic hormone secretion (SIADH). This chapter first reviews the regulatory mechanisms underlying water and sodium metabolism, the two major determinants of body fluid homeostasis. The major disorders of water metabolism causing hyperosmolality and hypoosmolality, DI and SIADH, are then discussed in detail, including the pathogenesis, differential diagnosis and treatment of these disorders.
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Brain volume regulation in response to changes in osmolality.
Neuroscience, 2010Co-Authors: Joseph G VerbalisAbstract:Hypoosmolality and hyperosmolality are relatively common clinical problems. Many different factors contribute to the substantial morbidity and mortality known to occur during states of altered osmotic homeostasis. The brain is particularly vulnerable to disturbances of body fluid osmolality. The most serious complications are associated with pathological changes in brain volume: brain edema during hypoosmolar states and brain dehydration during hyperosmolar states. Studies in animals have elucidated many of the mechanisms involved with brain adaptation to osmotic stresses, and indicate that it is a complex process involving transient changes in water content and sustained changes in electrolyte and organic osmolyte contents. Appreciation of the nature of the adaptation process, and conversely the deadaptation processes that occur after recovery from hypoosmolality and hyperosmolality, enables a better understanding of the marked variations in neurological sequelae that characterize hyperosmolar and hypoosmolar states, and provides a basis for more rational therapies.
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Microarray Analysis of Gene Expression in the Supraoptic Nucleus of Normoosmotic and Hypoosmotic Rats
Cellular and Molecular Neurobiology, 2006Co-Authors: Chunmei Yue, Joseph G Verbalis, Noriko Mutsuga, Harold GainerAbstract:1. Hypoosmolality produces a dramatic inhibition of vasopressin (VP) and oxytocin (OT) gene expression in the supraoptic nucleus (SON). This study examines the effect of sustained hypoosmolality on global gene expression in the OT and VP magnocellular neurons (MCNs) of the hypothalamo-neurohypophysial system (HNS), in order to detect novel genes in this system that might be involved in osmoregulation in the MCNs. 2. For this purpose, we used Affymetrix oligonucleotide arrays to analyze the expression of specific genes in laser microdissected rat SONs, and their changes in expression during chronic hypoosmolality. We identified over 40 genes that had three-fold or more greater expression in the SON versus total hypothalamus, and that also changed more than two fold in expression as a result of the chronic hypoosmolar treatment. These genes contained both novel as well as genes previously known to be present in the SON. All of the raw data for the genes that are expressed in the SON and altered by hypoosmolality can be found on the following NINDS website URL address: http://data.ninds.nih.gov/Gainer/Publications
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control of brain volume during hypoosmolality and hyperosmolality
Advances in Experimental Medicine and Biology, 2006Co-Authors: Joseph G VerbalisAbstract:Multiple studies over several decades have provided evidence that both electrolytes and organic osmolytes play crucial roles in regulating brain volume, both during increases as well as during decreases in extracellular fluid osmolality. In both situations, rapidly, and however, changes in brain electrolyte contents appear to occur more represent the first line of defense of brain volume during acute perturbations of body fluid tonicity, while organic osmolytes allow adaptation to more chronic perturbations. For both hyperosmolality and hypoosmolality, the rate of development of the disorder is an important determinant of neurological morbidity and mortality, since sufficiently rapid changes in tonicity can exceed the brain's capacity to regulate its volume leading to more severe degrees of brain edema or dehydration. Recovery from both hyper- and hypoosmolality requires reversal of the adaptive processes that enabled regulation of brain volume in response to the initial insult. However, adaptation and recovery are not symmetrical processes. Marked differences occur in the speed with which the brain is able to lose or to reaccumulate different types of solutes after recovery from chronic disturbances of body fluid tonicity. In general, accumulation, or reaccumulation, of organic solutes by brain tissue is a much slower process than volume regulatory losses of such solutes. As with the adaptation process, the rate of recovery is an important determinant of subsequent morbidity and mortality, since rapid corrections of osmolality can also exceed the capacity of the brain to readjust its solute content, and consequently its volume, back to normal levels. Whether or not transient excesses or deficiencies of either electrolytes or specific organic osmolytes in brain intracellular or extracellular fluid contribute to functional disturbances independently of changes in brain volume is an intriguing question that has not been sufficiently evaluated. Also remaining to be answered are questions regarding other physiological, pathophysiological, and pharmacological factors that either impair or enhance volume regulatory processes, and thereby modify the neurological manifestations accompanying disorders of body fluid osmolality in humans. Finally, a complete understanding of the cellular mechanisms underlying adaptation to and deadaptation from acute and chronic perturbations of body osmolality will be essential to design the most enlightened, and therefore appropriate, treatments for these disorders.
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regulation of gene expression in magnocellular neurons in rat supraoptic nucleus during sustained hypoosmolality
Endocrinology, 2005Co-Authors: Noriko Mutsuga, Joseph G Verbalis, Tal Shahar, Charlie C Xiang, Michael J Brownstein, Harold GainerAbstract:Hypoosmolality produces a dramatic inhibition of vasopressin (VP) and oxytocin gene expression in the supraoptic nucleus (SON). This study examines the effect of sustained hypoosmolality on global gene expression in the oxytocin and VP magnocellular neurons of the hypothalamo-neurohypophysial system, to identify genes associated with the magnocellular neuron’s adaptation to this physiological condition. Using laser microdissection of the SON, T7-based linear amplification of its RNA, and a 35,319-element cDNA microarray, we compare gene expression profiles between SONs in normoosmolar (control), 1-desamino-[8-d-arginine]-VP-treated normoosmolar, and hypoosmolar rats. We found 4959 genes with statistically significant differences in expression between normosmolar control and the hypoosmolar SONs, with 1564 of these differing in expression by more than 2-fold. These genes serve a wide variety of functions, and most were up-regulated in gene expression in hypoosmolar compared with control SONs. Of these, 90 ...
Dieter Häussinger - One of the best experts on this subject based on the ideXlab platform.
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Insulin induces swelling-dependent activation of the epidermal growth factor receptor in rat liver.
The Journal of biological chemistry, 2010Co-Authors: Roland Reinehr, Annika Sommerfeld, Dieter HäussingerAbstract:The aim of the study was to analyze whether the proliferative effects of insulin in rat liver involve cross-signaling toward the epidermal growth factor receptor (EGFR) and whether this is mediated by insulin-induced hepatocyte swelling. Studies were performed in the perfused rat liver and in primary rat hepatocytes. Insulin (35 nmol/liter) induced phosphorylation of the EGFR at position Tyr845 and Tyr1173, but not at Tyr1045, suggesting that EGF is not involved in insulin-induced EGFR activation. Insulin-induced EGFR phosphorylation and subsequent ERK1/2 phosphorylation were sensitive to bumetanide, indicating an involvement of insulin-induced hepatocyte swelling. In line with this, hypoosmotic (225 mosmol/liter) hepatocyte swelling also induced EGFR and ERK1/2 activation. Insulin- and Hypoosmolarity-induced EGFR activation were sensitive to inhibition by an integrin-antagonistic RGD peptide, an integrin β1 subtype-blocking antibody, and the c-Src inhibitor PP-2, indicating the involvement of the recently described integrin-dependent osmosensing/signaling pathway (Schliess, F., Reissmann, R., Reinehr, R., vom Dahl, S., and Haussinger, D. (2004) J. Biol. Chem. 279, 21294–21301). As shown by immunoprecipitation studies, insulin and Hypoosmolarity induced a rapid, RGD peptide-, integrin β1-blocking antibody and PP-2-sensitive association of c-Src with the EGFR. As for control, insulin-induced insulin receptor substrate-1 phosphorylation remained unaffected by the RGD peptide, PP-2, or inhibition of the EGFR tyrosine kinase activity by AG1478. Both insulin and Hypoosmolarity induced a significant increase in BrdU uptake in primary rat hepatocytes, which was sensitive to RGD peptide-, integrin β1-blocking antibody, PP-2, AG1478, and PD098059. It is concluded that insulin- or Hypoosmolarity-induced hepatocyte swelling triggers an integrin- and c-Src kinase-dependent EGFR activation, which may explain the proliferative effects of insulin.
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Hypoosmotic swelling affects zinc homeostasis in cultured rat astrocytes.
Glia, 2009Co-Authors: Caroline Kruczek, Freimut Schliess, Boris Görg, Verena Keitel, Elvis Pirev, Klaus D. Kröncke, Dieter HäussingerAbstract:Astrocyte swelling is observed in different types of brain injury including hepatic encephalopathy (HE). This study investigates the role of astrocyte swelling on Zn2+ homeostasis in hypoosmotically treated astrocytes by using the Zn2+ indicators Newport-Green, Zinquin, and RhodZin-3. Hypoosmolarity (205 mosmol/L) led to a persistent increase of the intracellular “free” Zn2+ concentration [Zn2+]i within 15 min, which was reversible after reinstitution of normoosmolarity (305 mosmol/L). The hypoosmotic [Zn2+]i increase was abolished in the presence of the Zn2+ chelator TPEN, the NMDA receptor antagonists MK-801 and AP5, the antioxidant epigallocatechin gallate, and the nitric oxide synthase inhibitors L-NMMA and TRIM. Hypoosmolarity triggered nuclear accumulation of the metal response element-binding transcription factor MTF-1 and the specificity protein Sp1 and expression of the mRNAs encoding metallothionein and the Sp1-regulated peripheral-type benzodiazepine receptor (PBR). These effects were abolished by the Zn2+ chelator TPEN. The data suggest that astrocyte swelling affects gene expression by modulation of [Zn2+]i. Whereas Zn2+-dependent upregulation of metallothionein may help to counteract excessive astrocyte swelling and production of reactive oxygen and nitrogen oxide species, stimulation of PBR expression may augment HE development. © 2008 Wiley-Liss, Inc.
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Cell hydration and mTOR‐dependent signalling
Acta Physiologica, 2006Co-Authors: Freimut Schliess, S. Vom Dahl, Lisa Richter, Dieter HäussingerAbstract:Insulin- and amino acid-induced signalling by the mammalian target of rapamycin (mTOR) involves hyperphosphorylation of the p70 ribosomal S6 protein kinase (p70S6-kinase) and the eukaryotic initiation factor 4E (eIF4E) binding protein 4E-BP1 and contributes to regulation of protein metabolism. This review considers the impact of cell hydration on mTOR-dependent signalling. Although hypoosmotic hepatocyte swelling in some instances activates p70S6-kinase, the Hypoosmolarity-induced proteolysis inhibition in perfused rat liver is insensitive to mTOR inhibition by rapamycin. Likewise, swelling-dependent proteolysis inhibition by insulin and swelling-independent proteolysis inhibition by leucine, a potent activator of p70S6-kinase and 4E-BP1 hyperphosphorylation, in perfused rat liver is insensitive to rapamycin, indicating that at least rapamycin-sensitive mTOR signalling is not involved. Hyperosmotic dehydration in different cell types produces inactivation of signalling components around mTOR, thereby attenuating insulin-induced glucose uptake, glycogen synthesis, and lipogenesis in adipocytes, and MAP-kinase phosphatase MKP-1 expression in hepatoma cells. Direct inactivation of mTOR, stimulation of the AMP-activated protein kinase, and the destabilization of individual proteins may impair mTOR signalling under dehydrating conditions. Further investigation of the crosstalk between the mTOR pathway(s) and hyperosmotic signalling will improve our understanding about the contribution of cell hydration changes in health and disease and will provide further rationale for fluid therapy of insulin-resistant states.
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Identification of osmosensitive and ammonia-regulated genes in rat astrocytes by Northern blotting and differential display reverse transcriptase-polymerase chain reaction.
Journal of hepatology, 2001Co-Authors: Ulrich Warskulat, Sabine Kreuels, Hans Werner Müller, Dieter HäussingerAbstract:Abstract Background/Aims : The hepatic encephalopathy (HE) is in part the result of astrocyte swelling with alterations of glial function. Detoxification of ammonia may be one mechanism by which astrocyte swelling is triggered in HE. Methods : The differential display polymerase chain reaction (DDRT-PCR) and Northern blot analysis were used for study the functional consequence of cell volume changes and ammonia on gene expression in primary rat astrocytes. Results : Differentially expressed cDNA products were identified with about 92% homology to genes coding for mouse proline rich protein expressed in brain (PRTB), rat clusterin, elongin, and human Kelch motif containing protein. As shown by Northern blot analysis, PRTB and clusterin mRNA levels were upregulated by 19–64% after 4–8 h by both ammonia and Hypoosmolarity. Elongin mRNA expression increased by 97% in response to ammonia but slightly by Hypoosmolarity. Further, hypoosmotic exposure for 1–24 hours but not ammonia led to an increase of 80% in KMCP mRNA levels. Conclusions : The identification of these genes offers the opportunity to identify unrecognized molecular mechanisms of HE. The finding that several genes are induced by both, Hypoosmolarity and ammonia, supports the view that astrocyte swelling is a major, but not the only pathogenetic event in HE.
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Hypoosmolarity influences the activity of transcription factor NF-κB in rat H4IIE hepatoma cells
FEBS letters, 1999Co-Authors: Manuela Michalke, Freimut Schliess, Alexandra Cariers, Dieter HäussingerAbstract:Abstract The influence of anisoosmolarity on NF-κB binding activity was studied in H4IIE rat hepatoma cells. Hypoosmolarity induced a sustained NF-κB binding activity whereas the hyperosmotic NF-κB response was only minor. Hypoosmotic NF-κB activation was accompanied by degradation of the inhibitory IκB-α. Protein kinase C, PI3-kinase, reactive oxygen intermediates and the proteasome apparently participate in mediating the hypoosmotic effect on NF-κB. Hypoosmolarity plus PMA induced, amplified and prolonged IκB-α degradation and NF-κB binding activity. Transforming growth factor β-induced apoptosis was diminished by Hypoosmolarity. However, this anti-apoptotic effect was probably not related to NF-κB activation.
Alain Lavoinne - One of the best experts on this subject based on the ideXlab platform.
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Osmotic stress, a proinflammatory signal in Caco-2 cells
Biochimie, 2004Co-Authors: Aurélie Hubert, Annie Husson, Arlette Chedeville, Bruno Cauliez, Alain LavoinneAbstract:Hyper- (450 mOsm/l) and hypoosmotic exposure (150 mOsm/l) of Caco-2 cells, a human intestinal epithelial cell line, induced a twofold- and a fivefold increase in the production of IL-8, a constitutively expressed cytokine, respectively. This was observed both in the presence or in the absence of added proinflammatory cytokines and the stimulatory effect of osmotic stress was additive to that induced by the cytokines. Thus, IL-8 production appeared minimal around isoosmolarity, i.e. 300 mOsm/l. Concerning the signalling pathway involved, specific inhibition of p38- or p42/44 MAP kinases decreased the IL-8 production by about 30% independently of the osmotic condition used. Inhibition of c-jun-NH2-terminal kinase (JNK) by using both dicoumarol and SP600125 totally inhibited the stimulatory effect of Hypoosmolarity. Moreover, Hypoosmolarity induced an about threefold increase in JNK activity demonstrating that JNK was specifically involved in the effect of Hypoosmolarity on IL-8 production. This is not the case for hyperosmolarity. Such an effect of osmotic stress was not restricted to IL-8, but was also observed on the production of IL-6, a non-constitutively expressed cytokine. Again, IL-6 production appeared minimal in isoosmotic condition. Taken together, these results demonstrate that osmotic stress is a proinflammatory signal in Caco-2 cells and suggest that an osmosensor might specifically exist in intestinal epithelial cells.
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Protein synthesis is involved in the modulation of the level of the phosphoenolpyruvate carboxykinase mRNA by changes in cell volume in isolated rat hepatocytes
FEBS letters, 1998Co-Authors: Muriel Quillard, Annie Husson, Arlette Chedeville, Alain Fairand, Alain LavoinneAbstract:Abstract The mechanism of action of hydration state was studied on phosphoenolpyruvate carboxykinase (PCK) gene expression in isolated rat hepatocytes. Hypoosmolarity decreased the level of the PCK mRNA after a lag period of about 60 min. The decreasing effect of Hypoosmolarity was totally blocked by inhibitors of both protein synthesis and gene transcription. Moreover, Hypoosmolarity specifically increased the synthesis of a 45 000 M r protein, which decreased in the presence of inhibitors of transcription. A close relationship between the synthesis of the 45 000 M r protein and the decrease in the PCK mRNA level was observed, suggesting that this protein might potentially be involved in the regulation of the level of the PCK mRNA by cell swelling.
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Cell swelling increased the α2-macroglobulin gene expression in cultured rat hepatocytes
FEBS letters, 1998Co-Authors: D. Meisse, Annie Husson, Sylvie Renouf, Alain LavoinneAbstract:The effect of cell swelling on the expression of the α2-macroglobulin (α2M) gene was studied in hepatocytes in culture. Hypoosmolarity induced an increase (3-fold increase) in the level of α2M mRNA through a corresponding stimulation of the rate of transcription of the α2M gene. The addition of raffinose (100 mM) corrected the effect of Hypoosmolarity at both mRNA and transcriptional level, demonstrating that cell swelling per se was responsible for the observed effect on the expression of the α2M gene. Moreover, the effect of cell swelling was additive to that of interleukin 6, a major mediator of the acute-phase response.
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Hypoosmolarity and glutamine increased the β-actin gene transcription in isolated rat hepatocytes
FEBS letters, 1996Co-Authors: Annie Husson, Muriel Quillard, Arlette Chedeville, Alain Fairand, Alain LavoinneAbstract:Abstract The mechanism of action of hydration state was studied on β-actin gene expression in isolated hepatocytes. Results obtained with Northern blot analysis and run on transcription assays show that Hypoosmolarity increased and hyperosmolarity decreased the β-actin mRNA level through a corresponding modulation of the rate of the gene transcription. Glutamine, which is known to induce cell swelling, also increased the β-actin mRNA level in a dose-dependent manner and induced a stimulation of the β-actin gene transcription. Thus, cell hydration state regulates gene expression in the liver through a transcriptional mechanism.
Harold Gainer - One of the best experts on this subject based on the ideXlab platform.
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Microarray Analysis of Gene Expression in the Supraoptic Nucleus of Normoosmotic and Hypoosmotic Rats
Cellular and Molecular Neurobiology, 2006Co-Authors: Chunmei Yue, Joseph G Verbalis, Noriko Mutsuga, Harold GainerAbstract:1. Hypoosmolality produces a dramatic inhibition of vasopressin (VP) and oxytocin (OT) gene expression in the supraoptic nucleus (SON). This study examines the effect of sustained hypoosmolality on global gene expression in the OT and VP magnocellular neurons (MCNs) of the hypothalamo-neurohypophysial system (HNS), in order to detect novel genes in this system that might be involved in osmoregulation in the MCNs. 2. For this purpose, we used Affymetrix oligonucleotide arrays to analyze the expression of specific genes in laser microdissected rat SONs, and their changes in expression during chronic hypoosmolality. We identified over 40 genes that had three-fold or more greater expression in the SON versus total hypothalamus, and that also changed more than two fold in expression as a result of the chronic hypoosmolar treatment. These genes contained both novel as well as genes previously known to be present in the SON. All of the raw data for the genes that are expressed in the SON and altered by hypoosmolality can be found on the following NINDS website URL address: http://data.ninds.nih.gov/Gainer/Publications
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regulation of gene expression in magnocellular neurons in rat supraoptic nucleus during sustained hypoosmolality
Endocrinology, 2005Co-Authors: Noriko Mutsuga, Joseph G Verbalis, Tal Shahar, Charlie C Xiang, Michael J Brownstein, Harold GainerAbstract:Hypoosmolality produces a dramatic inhibition of vasopressin (VP) and oxytocin gene expression in the supraoptic nucleus (SON). This study examines the effect of sustained hypoosmolality on global gene expression in the oxytocin and VP magnocellular neurons of the hypothalamo-neurohypophysial system, to identify genes associated with the magnocellular neuron’s adaptation to this physiological condition. Using laser microdissection of the SON, T7-based linear amplification of its RNA, and a 35,319-element cDNA microarray, we compare gene expression profiles between SONs in normoosmolar (control), 1-desamino-[8-d-arginine]-VP-treated normoosmolar, and hypoosmolar rats. We found 4959 genes with statistically significant differences in expression between normosmolar control and the hypoosmolar SONs, with 1564 of these differing in expression by more than 2-fold. These genes serve a wide variety of functions, and most were up-regulated in gene expression in hypoosmolar compared with control SONs. Of these, 90 ...
Christiane Lauriere - One of the best experts on this subject based on the ideXlab platform.
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involvement of mpk4 in osmotic stress response pathways in cell suspensions and plantlets of arabidopsis thaliana activation by Hypoosmolarity and negative role in hyperosmolarity tolerance
FEBS Letters, 2004Co-Authors: Mariejo Droillard, Marie Boudsocq, Helene Barbierbrygoo, Christiane LauriereAbstract:Three of the protein kinases activated by hypoosmotic stress in Arabidopsis thaliana cell suspensions were previously characterized [FEBS, 2002, 527, 43–50] as mitogen-activated protein (MAP) kinases and two of them corresponded to Arabidopsis mitogen-activated protein kinase 6 (MPK6) (44 kDa) and MPK3 (39 kDa). The third MAP kinase was identified here to MPK4, using a corresponding specific antibody. Like MPK6 and MPK3, MPK4 activity is clearly inhibited by apigenin and MPK4 activation by Hypoosmolarity needs upstream phosphorylation events. Activation of the 3 MAP kinases, MPK3, 4 and 6, was confirmed in plantlets submitted to hypoosmotic stress. The action of a biotic signal, flagellin, was also demonstrated to induce the activations of the 3 MAP kinases. Using the mutant displaying MPK4 gene inactivation, the independence of the MPK3 and MPK6 activations towards the presence of MPK4 was demonstrated, both in hypoosmotic and flagellin signalling pathways. Although MPK4 was not activated by hyperosmolarity in cell suspensions nor in seedlings, a possible negative regulation of hyperosmolarity resistance by MPK4 is suggested, based both on phenotype and downstream gene expression studies.
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Different protein kinase families are activated by osmotic stresses in Arabidopsis thaliana cell suspensions. Involvement of the MAP kinases AtMPK3 and AtMPK6.
FEBS Letters, 2002Co-Authors: Mariejo Droillard, Marie Boudsocq, Hélène Barbier-brygoo, Christiane LauriereAbstract:Five Ca(2+)-independent protein kinases were rapidly activated by hypoosmotic stress, moderate or high hyperosmolarity induced by several osmolytes, sucrose, mannitol or NaCl. Three of these kinases, transiently activated by Hypoosmolarity, recognised by anti-phosphorylated mitogen-activated protein (MAP) kinase antibodies, sensitive to a MAP kinase inhibitor and inactivated by the action of a tyrosine phosphatase, corresponded to MAP kinases. Using specific antibodies, two of the MAP kinases were identified as AtMPK6 and AtMPK3. The two other protein kinases, durably activated by high hyperosmolarity, did not belong to the MAP kinase family. Activation of AtMPK6 and AtMPK3 by Hypoosmolarity depended on upstream protein kinases sensitive to staurosporine and on calcium influx. In contrast, these two transduction steps were not involved in the activation of the two protein kinases activated by high hyperosmolarity.