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Am J Physiol Lung Cell Mol Physiol
2009 Mar 01;2963:L372-83. doi: 10.1152/ajplung.90437.2008.
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SARS-CoV proteins decrease levels and activity of human ENaC via activation of distinct PKC isoforms.
Ji HL
,
Song W
,
Gao Z
,
Su XF
,
Nie HG
,
Jiang Y
,
Peng JB
,
He YX
,
Liao Y
,
Zhou YJ
,
Tousson A
,
Matalon S
.
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Among the multiple organ disorders caused by the severe acute respiratory syndrome coronavirus (SARS-CoV), acute lung failure following atypical pneumonia is the most serious and often fatal event. We hypothesized that two of the hydrophilic structural coronoviral proteins (S and E) would regulate alveolar fluid clearance by decreasing the cell surface expression and activity of amiloride-sensitive epithelial sodium (Na(+)) channels (ENaC), the rate-limiting protein in transepithelial Na(+) vectorial transport across distallung epithelial cells. Coexpression of either S or E protein with human alpha-, beta-, and gamma-ENaC in Xenopus oocytes led to significant decreases of both amiloride-sensitive Na(+) currents and gamma-ENaC protein levels at their plasma membranes. S and E proteins decreased the rate of ENaC exocytosis and either had no effect (S) or decreased (E) rates of endocytosis. No direct interactions among SARS-CoV E protein with either alpha- or gamma-ENaC were indentified. Instead, the downregulation of ENaC activity by SARS proteins was partially or completely restored by administration of inhibitors of PKCalpha/beta1 and PKCzeta. Consistent with the whole cell data, expression of S and E proteins decreased ENaC single-channel activity in oocytes, and these effects were partially abrogated by PKCalpha/beta1 inhibitors. Finally, transfection of human airway epithelial (H441) cells with SARS E protein decreased whole cell amiloride-sensitive currents. These findings indicate that lung edema in SARS infection may be due at least in part to activation of PKC by SARS proteins, leading to decreasing levels and activity of ENaC at the apical surfaces of lung epithelial cells.
Awayda,
Specific and nonspecific effects of protein kinase C on the epithelial Na (+) channel.
2000, Pubmed,
Xenbase
Awayda,
Specific and nonspecific effects of protein kinase C on the epithelial Na (+) channel.
2000,
Pubmed
,
Xenbase
Awayda,
Protein kinase regulation of a cloned epithelial Na+ channel.
1996,
Pubmed
,
Xenbase
Burch,
Relative expression of the human epithelial Na+ channel subunits in normal and cystic fibrosis airways.
1995,
Pubmed
Canessa,
Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits.
1994,
Pubmed
,
Xenbase
Chen,
Inhibition of Na+ transport in lung epithelial cells by respiratory syncytial virus infection.
2009,
Pubmed
Chen,
Influenza virus inhibits ENaC and lung fluid clearance.
2004,
Pubmed
Chinet,
Mechanism of sodium hyperabsorption in cultured cystic fibrosis nasal epithelium: a patch-clamp study.
1994,
Pubmed
Dada,
Hypoxia-induced endocytosis of Na,K-ATPase in alveolar epithelial cells is mediated by mitochondrial reactive oxygen species and PKC-zeta.
2003,
Pubmed
Dascal,
The use of Xenopus oocytes for the study of ion channels.
1987,
Pubmed
,
Xenbase
Davis,
Leflunomide prevents alveolar fluid clearance inhibition by respiratory syncytial virus.
2006,
Pubmed
Davis,
Respiratory syncytial virus induces insensitivity to beta-adrenergic agonists in mouse lung epithelium in vivo.
2007,
Pubmed
Davis,
Post-infection A77-1726 blocks pathophysiologic sequelae of respiratory syncytial virus infection.
2007,
Pubmed
Davis,
Nucleotide-mediated inhibition of alveolar fluid clearance in BALB/c mice after respiratory syncytial virus infection.
2004,
Pubmed
Factor,
Adenovirus-mediated transfer of an Na+/K+-ATPase beta1 subunit gene improves alveolar fluid clearance and survival in hyperoxic rats.
2000,
Pubmed
Goldfarb,
Differential effects of Hsc70 and Hsp70 on the intracellular trafficking and functional expression of epithelial sodium channels.
2006,
Pubmed
,
Xenbase
Guo,
Nitric oxide inhibits Na+ absorption across cultured alveolar type II monolayers.
1998,
Pubmed
Hickman-Davis,
Reactive species mediate inhibition of alveolar type II sodium transport during mycoplasma infection.
2006,
Pubmed
Hummler,
Early death due to defective neonatal lung liquid clearance in alpha-ENaC-deficient mice.
1996,
Pubmed
,
Xenbase
Jain,
Expression of highly selective sodium channels in alveolar type II cells is determined by culture conditions.
2001,
Pubmed
Ji,
Delta-subunit confers novel biophysical features to alpha beta gamma-human epithelial sodium channel (ENaC) via a physical interaction.
2006,
Pubmed
Ji,
Peptide inhibition of constitutively activated epithelial Na(+) channels expressed in Xenopus oocytes.
1999,
Pubmed
,
Xenbase
Ji,
The cytosolic termini of the beta- and gamma-ENaC subunits are involved in the functional interactions between cystic fibrosis transmembrane conductance regulator and epithelial sodium channel.
2000,
Pubmed
,
Xenbase
Ji,
Up-regulation of acid-gated Na(+) channels (ASICs) by cystic fibrosis transmembrane conductance regulator co-expression in Xenopus oocytes.
2002,
Pubmed
,
Xenbase
Ji,
The role of Pre-H2 domains of alpha- and delta-epithelial Na+ channels in ion permeation, conductance, and amiloride sensitivity.
2004,
Pubmed
,
Xenbase
Johnson,
Functional ion channels in pulmonary alveolar type I cells support a role for type I cells in lung ion transport.
2006,
Pubmed
Johnson,
Alveolar epithelial type I cells contain transport proteins and transport sodium, supporting an active role for type I cells in regulation of lung liquid homeostasis.
2002,
Pubmed
Knight,
Liddle's syndrome mutations increase Na+ transport through dual effects on epithelial Na+ channel surface expression and proteolytic cleavage.
2006,
Pubmed
Kunzelmann,
Inhibition of airway Na+ transport by respiratory syncytial virus.
2007,
Pubmed
Kunzelmann,
Influenza virus inhibits amiloride-sensitive Na+ channels in respiratory epithelia.
2000,
Pubmed
Langloh,
Charged residues in the M2 region of alpha-hENaC play a role in channel conductance.
2000,
Pubmed
,
Xenbase
Lazrak,
cAMP-induced changes of apical membrane potentials of confluent H441 monolayers.
2003,
Pubmed
Liao,
Expression of SARS-coronavirus envelope protein in Escherichia coli cells alters membrane permeability.
2004,
Pubmed
Liu,
The sevenfold way of PKC regulation.
1998,
Pubmed
Matalon,
Invited review: biophysical properties of sodium channels in lung alveolar epithelial cells.
2002,
Pubmed
Matalon,
Sodium channels in alveolar epithelial cells: molecular characterization, biophysical properties, and physiological significance.
1999,
Pubmed
Matthay,
Lung epithelial fluid transport and the resolution of pulmonary edema.
2002,
Pubmed
McNicholas,
Diversity of channels generated by different combinations of epithelial sodium channel subunits.
1997,
Pubmed
,
Xenbase
Palmer-Densmore,
UTP-dependent inhibition of Na+ absorption requires activation of PKC in endometrial epithelial cells.
2002,
Pubmed
Peebles,
A mechanistic advance in understanding RSV pathogenesis, but still a long way from therapy.
2007,
Pubmed
Peiris,
Coronavirus as a possible cause of severe acute respiratory syndrome.
2003,
Pubmed
Pinto,
The M2 proton channels of influenza A and B viruses.
2006,
Pubmed
Sheng,
External nickel inhibits epithelial sodium channel by binding to histidine residues within the extracellular domains of alpha and gamma subunits and reducing channel open probability.
2002,
Pubmed
,
Xenbase
Stadler,
SARS--beginning to understand a new virus.
2003,
Pubmed
Stockand,
Differential effects of protein kinase C on the levels of epithelial Na+ channel subunit proteins.
2000,
Pubmed
,
Xenbase
Su,
Interregulation of proton-gated Na(+) channel 3 and cystic fibrosis transmembrane conductance regulator.
2006,
Pubmed
Vadász,
Thrombin impairs alveolar fluid clearance by promoting endocytosis of Na+,K+-ATPase.
2005,
Pubmed
Ware,
Alveolar fluid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome.
2001,
Pubmed
Wilson,
SARS coronavirus E protein forms cation-selective ion channels.
2004,
Pubmed
Wong,
The management of coronavirus infections with particular reference to SARS.
2008,
Pubmed
Yamagata,
Modulation of Na+ transport and epithelial sodium channel expression by protein kinase C in rat alveolar epithelial cells.
2005,
Pubmed
Yue,
Increased expression and activity of sodium channels in alveolar type II cells of hyperoxic rats.
1995,
Pubmed
Yue,
Mechanisms and sequelae of increased alveolar fluid clearance in hyperoxic rats.
1997,
Pubmed
