%0 Journal Article
%~ PubMed
%A Arnaiz, Isabel
%A Johnson, Mh
%A Cook, David I
%A Day, Margot L
%T Changing expression of chloride channels during pre-implantation mouse development.
%B Reproduction
%D 2013
%C United Kingdom
%I BioScientifica Ltd.
%V 145
%N 1
%P 73-84
%@ 1741-7899
%X 
%Z FOR Codes: 60103 60602 111404


%0 Journal Article
%~ PubMed
%A Campbell, Craig R
%A Voyles, Jamie
%A Cook, David I
%A Dinudom, Anuwat
%T Frog skin epithelium: Electrolyte transport and chytridiomycosis.
%B The international journal of biochemistry & cell biology
%D 2012
%C United Kingdom
%I Pergamon
%V 44
%N 3
%P 431-4
%@ 1357-2725
%X One unique physiological characteristic of frogs is that their main route for intake of water is across the skin. In these animals, the skin acts in concert with the kidney and urinary bladder to maintain electrolyte homeostasis. Water absorption across the skin is driven by the osmotic gradient that develops as a consequence of solute transport. Our recent study demonstrated that chytridiomycosis, an infection of amphibian skin by the fungal pathogen, Batrachochytrium dendrobatidis, inhibits epithelial Na(+) channels, attenuating Na(+) absorption through the skin. In frogs that become severely affected by this fungus, systemic depletion of Na(+), K(+) and Cl(-) is thought to cause deterioration of cardiac electrical function, leading to cardiac arrest. Here we review the ion transport mechanisms of frog skin, and discuss the effect of chytridiomycosis on these mechanisms.
%Z FOR Codes: 60602 602


%0 Journal Article
%~ PubMed
%A Lam, Yan Y
%A Ha, Connie W Y
%A Campbell, Craig R
%A Mitchell, Andrew J
%A Dinudom, Anuwat
%A Oscarsson, Jan
%A Cook, David I
%A Hunt, Nicholas H
%A Caterson, Ian D
%A Holmes, Andrew J
%A Storlien, Len H
%T Increased gut permeability and microbiota change associate with mesenteric fat inflammation and metabolic dysfunction in diet-induced obese mice.
%B PLoS One
%D 2012
%C United States
%I Public Library of Science
%V 7
%N 3
%P e34233
%@ 1932-6203
%X We investigated the relationship between gut health, visceral fat dysfunction and metabolic disorders in diet-induced obesity. C57BL/6J mice were fed control or high saturated fat diet (HFD). Circulating glucose, insulin and inflammatory markers were measured. Proximal colon barrier function was assessed by measuring transepithelial resistance and mRNA expression of tight-junction proteins. Gut microbiota profile was determined by 16S rDNA pyrosequencing. Tumor necrosis factor (TNF)-? and interleukin (IL)-6 mRNA levels were measured in proximal colon, adipose tissue and liver using RT-qPCR. Adipose macrophage infiltration (F4/80(+)) was assessed using immunohistochemical staining. HFD mice had a higher insulin/glucose ratio (P?=?0.020) and serum levels of serum amyloid A3 (131%; P?=?0.008) but reduced circulating adiponectin (64%; P?=?0.011). In proximal colon of HFD mice compared to mice fed the control diet, transepithelial resistance and mRNA expression of zona occludens 1 were reduced by 38% (P<0.001) and 40% (P?=?0.025) respectively and TNF-? mRNA level was 6.6-fold higher (P?=?0.037). HFD reduced Lactobacillus (75%; P<0.001) but increased Oscillibacter (279%; P?=?0.004) in fecal microbiota. Correlations were found between abundances of Lactobacillus (r?=?0.52; P?=?0.013) and Oscillibacter (r?=?-0.55; P?=?0.007) with transepithelial resistance of the proximal colon. HFD increased macrophage infiltration (58%; P?=?0.020), TNF-? (2.5-fold, P<0.001) and IL-6 mRNA levels (2.5-fold; P?=?0.008) in mesenteric fat. Increased macrophage infiltration in epididymal fat was also observed with HFD feeding (71%; P?=?0.006) but neither TNF-? nor IL-6 was altered. Perirenal and subcutaneous adipose tissue showed no signs of inflammation in HFD mice. The current results implicate gut dysfunction, and attendant inflammation of contiguous adipose, as salient features of the metabolic dysregulation of diet-induced obesity.
%Z FOR Codes: 60602 60106


%0 Journal Article
%~ PubMed
%A Hee, Leia
%A Dinudom, Anuwat
%A Mitchell, Andrew J
%A Grau, Georges E
%A Cook, David I
%A Hunt, Nicholas H
%A Ball, Helen J
%T Reduced activity of the epithelial sodium channel in malaria-induced pulmonary edema in mice.
%B International Journal for Parasitology
%D 2011
%C United Kingdom, Australia
%I Elsevier Ltd
%V 41
%N 1
%P 81-88
%@ 0020-7519
%X Lung complications during malaria infection can range from coughs and impairments in gas transfer to the development of acute respiratory distress syndrome (ARDS). Infecting C57BL/6 mice with Plasmodium berghei K173 strain (PbK) resulted in pulmonary oedema, capillaries congested with leukocytes and infected red blood cells (iRBCs), and leukocyte infiltration into the lungs. This new model of malaria-associated lung pathology, without any accompanying cerebral complications, allows the investigation of mechanisms leading to the lung disease. The activity of the amiloride-sensitive epithelial sodium channel (ENaC) in alveolar epithelial cells is decreased by several respiratory tract pathogens and this is suggested to contribute to pulmonary oedema. We show that PbK, a pathogen that remains in the circulation, also decreased the activity and expression of ENaC, suggesting that infectious agents can have indirect effects on ENaC activity in lung epithelial cells. The reduced ENaC activity may contribute to the pulmonary oedema induced by PbK malaria.
%Z FOR Codes: 110803 110707 111699


%0 Journal Article
%~ PubMed
%A Lee, Il-Ha
%A Song, Sung-Hee
%A Campbell, Craig R
%A Kumar, Sharad
%A Cook, David I
%A Dinudom, Anuwat
%T Regulation of the epithelial Na+ channel by the RH-domain of G protein-coupled receptor kinase, GRK2, and G{alpha}q/11.
%B The Journal of biological chemistry
%D 2011
%C United States
%I American Society for Biochemistry and Molecular Bi
%V 286
%N 22
%P 19259-69
%@ 0021-9258
%X The G protein-coupled receptor kinase (GRK2) belongs to a family of protein kinases that phosphorylates agonist-activated G protein-coupled receptors, leading to G protein-receptor uncoupling and termination of G protein signaling. GRK2 also contains a regulator of G protein signaling homology (RH) domain, which selectively interacts with ??-subunits of the Gq/11 family that are released during G protein-coupled receptor activation. We have previously reported that kinase activity of GRK2 up-regulates activity of the epithelial sodium channel (ENaC) in a Na(+) absorptive epithelium by blocking Nedd4-2-dependent inhibition of ENaC. In the present study, we report that GRK2 also regulates ENaC by a mechanism that does not depend on its kinase activity. We show that a wild-type GRK2 (wtGRK2) and a kinase-dead GRK2 mutant ((K220R)GRK2), but not a GRK2 mutant that lacks the C-terminal RH domain (??RH-GRK2) or a GRK2 mutant that cannot interact with G??q/11/14 ((D110A)GRK2), increase activity of ENaC. GRK2 up-regulates the basal activity of the channel as a consequence of its RH domain binding the ??-subunits of Gq/11. We further found that expression of constitutively active G??q/11 mutants significantly inhibits activity of ENaC. Conversely, co-expression of siRNA against G??q/11 increases ENaC activity. The effect of G??q on ENaC activity is not due to change in ENaC membrane expression and is independent of Nedd4-2. These findings reveal a novel mechanism by which GRK2 and Gq/11 ??-subunits regulate the activity ENaC.
%Z FOR Codes: 60602


%0 Journal Article
%~ PubMed
%A Boase, Natasha A
%A Rychkov, Grigori Y
%A Townley, Scott L
%A Dinudom, Anuwat
%A Candi, Eleanora
%A Voss, Anne K
%A Tsoutsman, Tatiana
%A Semsarian, Chris
%A Melino, Gerry
%A Koentgen, Frank
%A Cook, David I
%A Kumar, Sharad
%T Respiratory distress and perinatal lethality in Nedd4-2-deficient mice.
%B Nature Communications
%D 2011
%C United Kingdom
%I Nature Publishing Group
%V 2
%N 
%P 287
%@ 2041-1723
%X The epithelial sodium channel (ENaC) is essential for sodium homoeostasis in many epithelia. ENaC activity is required for lung fluid clearance in newborn animals and for maintenance of blood volume and blood pressure in adults. In vitro studies show that the ubiquitin ligase Nedd4-2 ubiquitinates ENaC to regulate its cell surface expression. Here we show that knockout of Nedd4-2 in mice leads to increased ENaC expression and activity in embryonic lung. This increased ENaC activity is the likely reason for premature fetal lung fluid clearance in Nedd4-2(-/-) animals, resulting in a failure to inflate lungs and perinatal lethality. A small percentage of Nedd4-2(-/-) animals survive up to 22 days, and these animals also show increased ENaC expression and develop lethal sterile inflammation of the lung. Thus, we provide critical in vivo evidence that Nedd4-2 is essential for correct regulation of ENaC expression, fetal and postnatal lung function and animal survival.
%Z FOR Codes: 110203 110203


%0 Journal Article
%~ PubMed
%A Ousingsawat, Jiraporn
%A Mirza, Myriam
%A Tian, Yuemin
%A Roussa, Eleni
%A Schreiber, Rainer
%A Cook, David I
%A Kunzelmann, Karl
%T Rotavirus toxin NSP4 induces diarrhea by activation of TMEM16A and inhibition of Na+ absorption.
%B Pflügers Archiv
%D 2011
%C Germany
%I Springer
%V 461
%N 5
%P 579-589
%@ 1432-2013
%X Rotavirus infection is the most frequent cause for severe diarrhea in infants, killing more than 600,000 every year. The nonstructural protein NSP4 acts as a rotavirus enterotoxin, inducing secretory diarrhea without any structural organ damage. Electrolyte transport was assessed in the colonic epithelium from pups and adult mice using Ussing chamber recordings. Western blots and immunocytochemistry was performed in intestinal tissues from wild-type and TMEM16A knockout mice. Ion channel currents were recorded using patch clamp techniques. We show that the synthetic NSP4(114-135) peptide uses multiple pro-secretory pathways to induce diarrhea, by activating the recently identified Ca2+ -activated Cl- channel TMEM16A, and by inhibiting Na+ absorption by the epithelial Na+ channel ENaC and the Na+ /glucose cotransporter SGLT1. Activation of secretion and inhibition of Na+ absorption by NSP4(114-135), respectively, could be potently suppressed by wheat germ agglutinin which probably competes with NSP4(114-135) for binding to an unknown glycolipid receptor. The present paper gives a clue as to mechanisms of rotavirus-induced diarrhea and suggests wheat germ agglutinin as a simple and effective therapy.
%Z FOR Codes: 60699


%0 Journal Article
%~ PubMed
%A Hu, Haibi
%A O'Mullane, Lauren M
%A Cummins, Michelle M
%A Campbell, Craig R
%A Hosoda, Yutaka
%A Poronnik, Philip
%A Dinudom, Anuwat
%A Cook, David I
%T Negative regulation of Ca(2+) influx during P2Y(2) purinergic receptor activation is mediated by Gbetagamma-subunits.
%B Cell Calcium
%D 2010
%C United States
%I Elsevier Science
%V 47
%N 1
%P 55-64
%@ 1532-1991
%X We have previously reported that P2Y(2) purinoceptors and muscarinic M(3) receptors trigger Ca(2+) responses in HT-29 cells that differ in their timecourse, the Ca(2+) response to P2Y(2) receptor activation being marked by a more rapid decline of intracellular Ca(2+) concentration ([Ca(2+)](i)) after the peak response and that this rapid decline of [Ca(2+)](i) was slowed in cells expressing heterologous beta-adrenergic receptor kinase (betaARK). In the present study, we demonstrate that, during P2Y(2) receptor activation, betaARK expression increases the rate of Gd(3+)-sensitive Mn(2+) influx, a measure of the rate of store-operated Ca(2+) entry from the extracellular space, during P2Y(2) activation and that this effect of betaARK is mimicked by exogenous alpha-subunits of G(q), G(11) and G(i2). The effect of betaARK on the rate of Mn(2+) influx is thus attributable to its ability to scavenge G protein betagamma-subunits released during activation of P2Y(2) receptor. We further find that the effect of betaARK on the rate of Mn(2+) influx during P2Y(2) receptor activation can be overcome by arachidonic acid. In addition, the UTP-induced Mn(2+) influx rate was significantly increased by inhibitors of phospholipase A(2) (PLA(2)) and an siRNA directed against PLA(2)beta, but not by an siRNA directed against PLA(2)alpha or by inhibitors of arachidonic acid metabolism. These findings provide evidence for the existence of a P2Y(2) receptor-activated signalling system that acts in parallel with depletion of intracellular Ca(2+) stores to inhibit Ca(2+) influx across the cell membrane. This signalling process is mediated via Gbetagamma and involves PLA(2)beta and arachidonic acid.
%Z FOR Codes: 111601


%0 Journal Article
%~ PubMed
%A Voyles, Jamie
%A Young, Sam
%A Berger, Lee
%A Campbell, Craig
%A Voyles, Wyatt F
%A Dinudom, Anuwat
%A Cook, David
%A Webb, Rebecca
%A Alford, Ross A
%A Skerratt, Lee F
%A Speare, Rick
%T Pathogenesis of chytridiomycosis, a cause of catastrophic amphibian declines.
%B Science
%D 2009
%C United States
%I American Association for the Advancement of Scienc
%V 326
%N 5952
%P 582-585
%@ 1095-9203
%X The pathogen Batrachochytrium dendrobatidis (Bd), which causes the skin disease chytridiomycosis, is one of the few highly virulent fungi in vertebrates and has been implicated in worldwide amphibian declines. However, the mechanism by which Bd causes death has not been determined. We show that Bd infection is associated with pathophysiological changes that lead to mortality in green tree frogs (Litoria caerulea). In diseased individuals, electrolyte transport across the epidermis was inhibited by >50%, plasma sodium and potassium concentrations were respectively reduced by approximately 20% and approximately 50%, and asystolic cardiac arrest resulted in death. Because the skin is critical in maintaining amphibian homeostasis, disruption to cutaneous function may be the mechanism by which Bd produces morbidity and mortality across a wide range of phylogenetically distant amphibian taxa.
%Z FOR Codes: 606


%0 Journal Article
%~ PubMed
%A O'Mullane, Lauren M
%A Cook, David I
%A Dinudom, Anuwat
%T Purinergic regulation of the epithelial Na+ channel.
%B Clinical and experimental pharmacology & physiology
%D 2009
%C Australia
%I Wiley-Blackwell Publishing Asia
%V 36
%N 10
%P 1016-22
%@ 1440-1681
%X 1. The epithelial Na(+) channel (ENaC) is a major conductive pathway that transports Na(+) across the apical membrane of the distal nephron, the respiratory tract, the distal colon and the ducts of exocrine glands. The ENaC is regulated by hormonal and humoral factors, including extracellular nucleotides that are available from the epithelial cells themselves. 2. Extracellular nucleotides, via the P2Y2 receptors (P2Y2Rs) at the basolateral and apical membrane of the epithelia, trigger signalling systems that inhibit the activity of the ENaC and activate Ca(2+) -dependent Cl(-) secretion. 3. Recent data from our laboratory suggest that stimulation of the P2Y2Rs at the basolateral membrane inhibits ENaC activity by a signalling mechanism that involves G beta gamma subunits freed from a pertussis toxin (PTX)-sensitive G-protein and phospholipase C (PLC) beta 4. A similar signalling mechanism is also partially responsible for inhibition of the ENaC during activation of apical P2Y2Rs. 4. Stimulation of apical P2Y2Rs also activates an additional signalling mechanism that inhibits the ENaC and involves the activated Galpha subunit of a PTX-insensitive G-protein and activation of an unidentified PLC. The effect of this PTX-insensitive system requires the activity of the basolateral Na(+)/K(+)/2Cl(-) cotransporter.
%Z FOR Codes: 60602


%0 Journal Article
%~ PubMed
%A Lee, Il-Ha
%A Campbell, Craig R
%A Song, Sung-Hee
%A Day, Margot L
%A Kumar, Sharad
%A Cook, David I
%A Dinudom, Anuwat
%T The activity of the epithelial sodium channels is regulated by caveolin-1 via a Nedd4-2-dependent mechanism.
%B Journal of Biological Chemistry
%D 2009
%C United States
%I American Society for Biochemistry and Molecular Bi
%V 284
%N 19
%P 12663-12669
%@ 0021-9258
%X It has recently been shown that the epithelial Na(+) channel (ENaC) is compartmentalized in caveolin-rich lipid rafts and that pharmacological depletion of membrane cholesterol, which disrupts lipid raft formation, decreases the activity of ENaC. Here we show, for the first time, that a signature protein of caveolae, caveolin-1 (Cav-1), down-regulates the activity and membrane surface expression of ENaC. Physical interaction between ENaC and Cav-1 was also confirmed in a coimmunoprecipitation assay. We found that the effect of Cav-1 on ENaC requires the activity of Nedd4-2, a ubiquitin protein ligase of the Nedd4 family, which is known to induce ubiquitination and internalization of ENaC. The effect of Cav-1 on ENaC requires the proline-rich motifs at the C termini of the beta- and gamma-subunits of ENaC, the binding motifs that mediate interaction with Nedd4-2. Taken together, our data suggest that Cav-1 inhibits the activity of ENaC by decreasing expression of ENaC at the cell membrane via a mechanism that involves the promotion of Nedd4-2-dependent internalization of the channel.
%Z FOR Codes: 60602 111601


%0 Journal Article
%~ PubMed
%A Lee, Il-Ha
%A Campbell, Craig R
%A Cook, David I
%A Dinudom, Anuwat
%T Regulation of epithelial Na+ channels by aldosterone: role of Sgk1.
%B Clinical and experimental pharmacology & physiology
%D 2008
%C Australia
%I Wiley-Blackwell
%V 35
%N 2
%P 235-241
%@ 0305-1870
%X 1. The epithelial sodium channel (ENaC) is tightly regulated by hormonal and humoral factors, including cytosolic ion concentration and glucocorticoid and mineralocorticoid hormones. Many of these regulators of ENaC control its activity by regulating its surface expression via neural precursor cell-expressed developmentally downregulated (gene 4) protein (Nedd4-2). 2. During the early phase of aldosterone action, Nedd4-2-dependent downregulation of ENaC is inhibited by the serum- and glucocorticoid-induced kinase 1 (Sgk1). 3. Sgk1 phosphorylates Nedd4-2. Subsequently, phosphorylated Nedd4-2 binds to the 14-3-3 protein and, hence, reduces binding of Nedd4-2 to ENaC. 4. Nedd4-2 is also phosphorylated by protein kinase B (Akt1). Both Sgk1 and Akt1 are part of the insulin signalling pathway that increases transepithelial Na(+) absorption by inhibiting Nedd4-2 and activating ENaC.
%Z FOR Codes: 111601 111599


%0 Journal Article
%~ Isi
%A Dinudom, A
%A Rauh, R
%A Korbmacher, C
%A Cook, DI
%A Farman, N
%A Lee, IH
%A Wielputz, MO
%A Boulkroun, S
%T (NDRG2) stimulates amiloride-sensitive Na+ currents in Xenopus laevis oocytes and fisher rat thyroid cells
%B JOURNAL OF BIOLOGICAL CHEMISTRY
%D 2007
%C United States
%I American Society for Biochemistry and Molecular Bi
%V 282
%N 38
%P 28264-28273
%@ 0021-9258
%X 
%Z FOR Codes:


%0 Journal Article
%~ PubMed
%A Lee, Il-Ha
%A Dinudom, Anuwat
%A Sanchez-Perez, Angeles
%A Kumar, Sharad
%A Cook, David I
%T Akt mediates the effect of insulin on epithelial sodium channels by inhibiting Nedd4-2.
%B The Journal of biological chemistry
%D 2007
%C Bethesda MD, USA
%I The American Society for Biochemistry and Molecula
%V 282
%N 
%P 29866-73
%@ 1083-351X
%X The epithelial sodium channel (ENaC) plays an important role in transepithelial Na(+) absorption; hence its function is essential for maintaining Na(+) and fluid homeostasis and regulating blood pressure. Insulin is one of the hormones that regulates activity of ENaC. In this study, we investigated the contribution of two related protein kinases, Akt (also known as protein kinase B) and the serum- and glucocorticoid-dependent kinase (Sgk), on insulin-induced ENaC activity in Fisher rat thyroid cells expressing ENaC. Overexpression of Akt1 or Sgk1 significantly increased ENaC activity, whereas expression of a dominant-negative construct of Akt1, Akt1(K179M), decreased basal activity of ENaC. Inhibition of the endogenous expression of Akt1 and Sgk1 by short interfering RNA not only inhibited ENaC but also disrupted the stimulatory effect on ENaC of insulin and of the downstream effectors of insulin, phosphatidylinositol 3-kinase and PDK1. Conversely, overexpression of Akt1 or Sgk1 increased expression of ENaC at the cell membrane and overcame the inhibitory effect of Nedd4-2 on ENaC. Furthermore, mutation of consensus phosphorylation sites on Nedd4-2 for Akt1 and Sgk1, Ser(342) and Ser(428), completely abolished the inhibitory effect of Sgk1 and Akt1 on Nedd4-2 action. Together these data suggest that both Akt and Sgk are components of an insulin signaling pathway that increases Na(+) absorption by up-regulating membrane expression of ENaC via a regulatory system that involves inhibition of Nedd4-2.
%Z FOR Codes:


%0 Book Section
%A Keech, Anthony
%A Wonders, Susan M
%A Cook, David
%A Pike, Rhana
%A Gebski, Val
%T Balancing the outcomes: reporting harms (adverse events)
%B Interpreting and reporting clinical trials: A guide to the CONSORT statement and the principles of randomised controlled trials
%D 2007
%C Australia
%I Australasian Medical Publishing Company Ltd.
%V 
%N 
%P 132-142
%@ 978-0-977-57864-1
%E Pike, Rhana
%E Keech, Anthony
%E Gebski, Val
%X 
%Z FOR Codes:


%0 Journal Article
%~ PubMed
%A Sanchez-Perez, Angeles
%A Kumar, Sharad
%A Cook, David I
%T GRK2 interacts with and phosphorylates Nedd4 and Nedd4-2.
%B Biochemical and biophysical research communications
%D 2007
%C United States
%I Academic Press
%V 359
%N 3
%P 611-615
%@ 1090-2104
%X Epithelial Na(+) channels (ENaC) mediate the transport of sodium (Na) across epithelia in the kidney, gut, and lungs and are required for blood pressure regulation. They are inhibited by ubiquitin protein ligases, such as Nedd4 and Nedd4-2, which bind to proline-rich motifs (PY motifs) present in the C-termini of ENaC subunits. Loss of inhibition leads to hypertension. ENaC channels are maintained in the active state by G-protein-coupled receptor kinase 2 (GRK2), an enzyme implicated in the development of essential hypertension. Here, we report that GRK2 interacts not only with ENaC, but also with both Nedd4 and Nedd4-2. Additionally, GRK2 is capable of phosphorylating both Nedd4 and Nedd4-2 at multiple sites. Of possible significance is the phosphorylation of the threonine at position 466 in Nedd4, which is located in the area of the ww3 domain that binds ENaC. These results support and extend the role of GRK2 in sodium transport regulation.
%Z FOR Codes:


%0 Journal Article
%~ PubMed
%A Kunzelmann, Karl
%A Sun, Jane
%A Meanger, Jayesh
%A King, Nicholas J
%A Cook, David I
%T Inhibition of airway Na+ transport by respiratory syncytial virus.
%B Journal of virology
%D 2007
%C US
%I American Society for Microbiology
%V 81
%N 8
%P 3714-20
%@ 0022-538X
%X In previous studies, we have shown that two major respiratory pathogens, influenza virus and parainfluenza virus, produce acute alterations in ion transport upon contacting the apical membrane of the respiratory epithelium. In the present study, we examine the effects on ion transport by the mouse tracheal epithelium of a third major respiratory pathogen, respiratory syncytial virus (RSV). RSV infections are associated with fluid accumulation in the respiratory tract and cause illnesses that range in severity from rhinitis, sinusitis, otitis media, and bronchitis to bronchiolitis and pneumonia. We find that within minutes of RSV contacting the apical membrane; it inhibits amiloride-sensitive Na+ transport by the epithelium. This effect is mediated by protein kinase C and is reproduced by recombinant viral F (fusion) protein. Since this inhibition is not accompanied by any alteration in the epithelial responses to carbachol or to forskolin plus 3-isobutyl-1-methylxanthine (IBMX), it is not due to a nonspecific toxic action of the virus. The inhibition also appears to require Toll-like receptor 4 and the presence of asialogangliosides in the apical membrane. Since the concentration range over which this inhibition is observed (10(2) to 10(5) PFU/ml) is comparable to the viral concentrations observed in clinical and experimental RSV infections, it seems likely that direct inhibition by the virus of epithelial Na+ transport may contribute to the fluid accumulation that is observed in RSV infections.
%Z FOR Codes: 110804


%0 Book Section
%A Cook, David
%A Gebski, Val
%A Keech, Anthony
%T Subgroup analysis in clinical trials
%B Interpreting and reporting clinical trials: A guide to the CONSORT statement and the principles of randomised controlled trials
%D 2007
%C Australia
%I Australasian Medical Publishing Company Ltd.
%V 
%N 
%P 105-113
%@ 978-0-977-57864-1
%E Pike, Rhana
%E Keech, Anthony
%E Gebski, Val
%X 
%Z FOR Codes:


%0 Journal Article
%~ PubMed
%A Arthur, Jonathan W
%A Sanchez-Perez, Angeles
%A Cook, David I
%T Scoring of predicted GRK2 phosphorylation sites in Nedd4-2.
%B Bioinformatics (Oxford, England)
%D 2006
%C United Kingdom
%I Oxford University Press
%V 22
%N 
%P 2192-5
%@ 1367-4803
%X Epithelial Na(+) channels (ENaC) mediate the transport of sodium (Na) across epithelia in the kidney, gut and lungs and are required for blood pressure regulation. They are inhibited by ubiquitin protein ligases, such as Nedd4-2. These ligases bind to proline-rich motifs (PY motifs) present in the C-termini of ENaC subunits. Loss of this inhibition leads to hypertension. We have previously reported that ENaC channels are maintained in the active state by the G protein coupled receptor kinase, GRK2. The enzyme has been implicated in the development of essential hypertension [R. D. Feldman (2002) Mol. Pharmacol., 61, 707-709]. Additional findings in our lab pointed towards a possible role for GRK2 in the phosphorylation and inactivation of Nedd4-2.
%Z FOR Codes: 111601


%0 Journal Article
%~ Isi
%A Rauh, R.
%A Dinudom, A.
%A Fotia, A. B.
%A Paulides, M.
%A Kumar, S.
%A Korbmacher, C.
%A Cook, D. I.
%T Stimulation of the epithelial sodium channel (ENaC) by the serum- and glucocorticoid-inducible kinase (Sgk) involves the PY motifs of the channel but is independent of sodium feedback inhibition.
%B Pflugers Archiv-European Journal of Physiology
%D 2006
%C Germany
%I Springer-Verlag
%V 452
%N 3
%P 290-299
%@ 0031-6768
%X 
%Z FOR Codes:


%0 Journal Article
%~ Isi
%A Fotia, A. B.
%A Cook, D. I.
%A Kumar, S.
%T The ubiquitin-protein ligases Nedd4 and Nedd4-2 show similar ubiquitin-conjugating enzyme specificities.
%B International Journal of Biochemistry & Cell Biology
%D 2006
%C United Kingdom
%I Pergamon
%V 38
%N 3
%P 472-479
%@ 1357-2725
%X 
%Z FOR Codes: