SARS-CoV proteins decrease levels and activity of human ENaC via activation of distinct PKC isoforms.
Identifieur interne : 002A26 ( Main/Curation ); précédent : 002A25; suivant : 002A27SARS-CoV proteins decrease levels and activity of human ENaC via activation of distinct PKC isoforms.
Auteurs : Hong-Long Ji [États-Unis] ; Weifeng Song ; Zhiqian Gao ; Xue-Feng Su ; Hong-Guang Nie ; Yi Jiang ; Ji-Bin Peng ; Yu-Xian He ; Ying Liao ; Yong-Jian Zhou ; Albert Tousson ; Sadis MatalonSource :
- American journal of physiology. Lung cellular and molecular physiology [ 1040-0605 ] ; 2009.
Descripteurs français
- KwdFr :
- Activation enzymatique, Amiloride (pharmacologie), Animaux, Canaux sodium épithéliaux (génétique), Canaux sodium épithéliaux (métabolisme), Endocytose, Exocytose, Expression des gènes, Femelle, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (génétique), Glycoprotéines membranaires (métabolisme), Humains, Inhibiteurs de protéines kinases (pharmacologie), Isoenzymes (antagonistes et inhibiteurs), Isoenzymes (métabolisme), Lignée cellulaire, Lésion pulmonaire aigüe (étiologie), Oedème pulmonaire (étiologie), Ovocytes (métabolisme), Protéine kinase C (antagonistes et inhibiteurs), Protéine kinase C (métabolisme), Protéines de l'enveloppe virale (génétique), Protéines de l'enveloppe virale (métabolisme), Protéines recombinantes (génétique), Protéines recombinantes (métabolisme), Protéines virales (génétique), Protéines virales (métabolisme), Techniques de patch-clamp, Techniques in vitro, Transfection, Virus du SRAS (génétique), Virus du SRAS (métabolisme), Virus du SRAS (pathogénicité), Xenopus.
- MESH :
- antagonistes et inhibiteurs : Isoenzymes, Protéine kinase C.
- génétique : Canaux sodium épithéliaux, Glycoprotéines membranaires, Protéines de l'enveloppe virale, Protéines recombinantes, Protéines virales, Virus du SRAS.
- métabolisme : Canaux sodium épithéliaux, Glycoprotéines membranaires, Isoenzymes, Ovocytes, Protéine kinase C, Protéines de l'enveloppe virale, Protéines recombinantes, Protéines virales, Virus du SRAS.
- pathogénicité : Virus du SRAS.
- pharmacologie : Amiloride, Inhibiteurs de protéines kinases.
- étiologie : Lésion pulmonaire aigüe, Oedème pulmonaire.
- Activation enzymatique, Animaux, Endocytose, Exocytose, Expression des gènes, Femelle, Glycoprotéine de spicule des coronavirus, Humains, Lignée cellulaire, Techniques de patch-clamp, Techniques in vitro, Transfection, Xenopus.
English descriptors
- KwdEn :
- Acute Lung Injury (etiology), Amiloride (pharmacology), Animals, Cell Line, Endocytosis, Enzyme Activation, Epithelial Sodium Channels (genetics), Epithelial Sodium Channels (metabolism), Exocytosis, Female, Gene Expression, Humans, In Vitro Techniques, Isoenzymes (antagonists & inhibitors), Isoenzymes (metabolism), Membrane Glycoproteins (genetics), Membrane Glycoproteins (metabolism), Oocytes (metabolism), Patch-Clamp Techniques, Protein Kinase C (antagonists & inhibitors), Protein Kinase C (metabolism), Protein Kinase Inhibitors (pharmacology), Pulmonary Edema (etiology), Recombinant Proteins (genetics), Recombinant Proteins (metabolism), SARS Virus (genetics), SARS Virus (metabolism), SARS Virus (pathogenicity), Spike Glycoprotein, Coronavirus, Transfection, Viral Envelope Proteins (genetics), Viral Envelope Proteins (metabolism), Viral Proteins (genetics), Viral Proteins (metabolism), Xenopus.
- MESH :
- chemical , antagonists & inhibitors : Isoenzymes, Protein Kinase C.
- chemical , genetics : Epithelial Sodium Channels, Membrane Glycoproteins, Recombinant Proteins, Viral Envelope Proteins, Viral Proteins.
- chemical , metabolism : Epithelial Sodium Channels, Isoenzymes, Membrane Glycoproteins, Protein Kinase C, Recombinant Proteins, Viral Envelope Proteins, Viral Proteins.
- chemical , pharmacology : Amiloride, Protein Kinase Inhibitors.
- etiology : Acute Lung Injury, Pulmonary Edema.
- genetics : SARS Virus.
- metabolism : Oocytes, SARS Virus.
- pathogenicity : SARS Virus.
- Animals, Cell Line, Endocytosis, Enzyme Activation, Exocytosis, Female, Gene Expression, Humans, In Vitro Techniques, Patch-Clamp Techniques, Spike Glycoprotein, Coronavirus, Transfection, Xenopus.
Abstract
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 distal lung 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.
DOI: 10.1152/ajplung.90437.2008
PubMed: 19112100
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pubmed:19112100Le document en format XML
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<term>Amiloride (pharmacology)</term>
<term>Animals</term>
<term>Cell Line</term>
<term>Endocytosis</term>
<term>Enzyme Activation</term>
<term>Epithelial Sodium Channels (genetics)</term>
<term>Epithelial Sodium Channels (metabolism)</term>
<term>Exocytosis</term>
<term>Female</term>
<term>Gene Expression</term>
<term>Humans</term>
<term>In Vitro Techniques</term>
<term>Isoenzymes (antagonists & inhibitors)</term>
<term>Isoenzymes (metabolism)</term>
<term>Membrane Glycoproteins (genetics)</term>
<term>Membrane Glycoproteins (metabolism)</term>
<term>Oocytes (metabolism)</term>
<term>Patch-Clamp Techniques</term>
<term>Protein Kinase C (antagonists & inhibitors)</term>
<term>Protein Kinase C (metabolism)</term>
<term>Protein Kinase Inhibitors (pharmacology)</term>
<term>Pulmonary Edema (etiology)</term>
<term>Recombinant Proteins (genetics)</term>
<term>Recombinant Proteins (metabolism)</term>
<term>SARS Virus (genetics)</term>
<term>SARS Virus (metabolism)</term>
<term>SARS Virus (pathogenicity)</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Transfection</term>
<term>Viral Envelope Proteins (genetics)</term>
<term>Viral Envelope Proteins (metabolism)</term>
<term>Viral Proteins (genetics)</term>
<term>Viral Proteins (metabolism)</term>
<term>Xenopus</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Activation enzymatique</term>
<term>Amiloride (pharmacologie)</term>
<term>Animaux</term>
<term>Canaux sodium épithéliaux (génétique)</term>
<term>Canaux sodium épithéliaux (métabolisme)</term>
<term>Endocytose</term>
<term>Exocytose</term>
<term>Expression des gènes</term>
<term>Femelle</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires (génétique)</term>
<term>Glycoprotéines membranaires (métabolisme)</term>
<term>Humains</term>
<term>Inhibiteurs de protéines kinases (pharmacologie)</term>
<term>Isoenzymes (antagonistes et inhibiteurs)</term>
<term>Isoenzymes (métabolisme)</term>
<term>Lignée cellulaire</term>
<term>Lésion pulmonaire aigüe (étiologie)</term>
<term>Oedème pulmonaire (étiologie)</term>
<term>Ovocytes (métabolisme)</term>
<term>Protéine kinase C (antagonistes et inhibiteurs)</term>
<term>Protéine kinase C (métabolisme)</term>
<term>Protéines de l'enveloppe virale (génétique)</term>
<term>Protéines de l'enveloppe virale (métabolisme)</term>
<term>Protéines recombinantes (génétique)</term>
<term>Protéines recombinantes (métabolisme)</term>
<term>Protéines virales (génétique)</term>
<term>Protéines virales (métabolisme)</term>
<term>Techniques de patch-clamp</term>
<term>Techniques in vitro</term>
<term>Transfection</term>
<term>Virus du SRAS (génétique)</term>
<term>Virus du SRAS (métabolisme)</term>
<term>Virus du SRAS (pathogénicité)</term>
<term>Xenopus</term>
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<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Isoenzymes</term>
<term>Protein Kinase C</term>
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<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Epithelial Sodium Channels</term>
<term>Membrane Glycoproteins</term>
<term>Recombinant Proteins</term>
<term>Viral Envelope Proteins</term>
<term>Viral Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Epithelial Sodium Channels</term>
<term>Isoenzymes</term>
<term>Membrane Glycoproteins</term>
<term>Protein Kinase C</term>
<term>Recombinant Proteins</term>
<term>Viral Envelope Proteins</term>
<term>Viral Proteins</term>
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<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Amiloride</term>
<term>Protein Kinase Inhibitors</term>
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<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Isoenzymes</term>
<term>Protéine kinase C</term>
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<keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Acute Lung Injury</term>
<term>Pulmonary Edema</term>
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<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term>
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<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Canaux sodium épithéliaux</term>
<term>Glycoprotéines membranaires</term>
<term>Protéines de l'enveloppe virale</term>
<term>Protéines recombinantes</term>
<term>Protéines virales</term>
<term>Virus du SRAS</term>
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<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Oocytes</term>
<term>SARS Virus</term>
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<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Canaux sodium épithéliaux</term>
<term>Glycoprotéines membranaires</term>
<term>Isoenzymes</term>
<term>Ovocytes</term>
<term>Protéine kinase C</term>
<term>Protéines de l'enveloppe virale</term>
<term>Protéines recombinantes</term>
<term>Protéines virales</term>
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<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Virus du SRAS</term>
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<term>Inhibiteurs de protéines kinases</term>
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<term>Oedème pulmonaire</term>
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<term>Cell Line</term>
<term>Endocytosis</term>
<term>Enzyme Activation</term>
<term>Exocytosis</term>
<term>Female</term>
<term>Gene Expression</term>
<term>Humans</term>
<term>In Vitro Techniques</term>
<term>Patch-Clamp Techniques</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Transfection</term>
<term>Xenopus</term>
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<keywords scheme="MESH" xml:lang="fr"><term>Activation enzymatique</term>
<term>Animaux</term>
<term>Endocytose</term>
<term>Exocytose</term>
<term>Expression des gènes</term>
<term>Femelle</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Techniques de patch-clamp</term>
<term>Techniques in vitro</term>
<term>Transfection</term>
<term>Xenopus</term>
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<front><div type="abstract" xml:lang="en">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 distal lung 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.</div>
</front>
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