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Essential structural features of TNF-? lectin-like domain derived peptides for activation of amiloride-sensitive sodium current in A549 cells.


ABSTRACT: The amiloride-sensitive epithelial sodium channel (ENaC) plays a prominent role in sodium uptake from alveolar fluid and is the major component in alveolar fluid clearance in normal and diseased lungs. The lectin-like domain of TNF-? has been shown to activate amiloride-sensitive sodium uptake in type II alveolar epithelial cells. Therefore, several synthetic peptides that mimic the lectin-like domain of TNF-? (TIP) were synthesized and their ability to enhance sodium current through ENaC was studied in A549 cells with the patch clamp technique. Our data suggest that a free positively charged N-terminal amino group on residue 1 and/or a free negatively charged carboxyl group on residue 17 of the TIP peptide is essential for the ENaC-activating effect. Ventilation strategies apart, no standard treatment exists for pulmonary permeability edema. Therefore, novel therapies activating sodium uptake from the alveolar fluid via ENaC could improve clinical outcome.

SUBMITTER: Hazemi P 

PROVIDER: S-EPMC2996585 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Essential structural features of TNF-α lectin-like domain derived peptides for activation of amiloride-sensitive sodium current in A549 cells.

Hazemi Parastoo P   Tzotzos Susan J SJ   Fischer Bernhard B   Andavan Gowri Shankar Bagavananthem GS   Fischer Hendrik H   Pietschmann Helmut H   Lucas Rudolf R   Lemmens-Gruber Rosa R  

Journal of medicinal chemistry 20101027 22


The amiloride-sensitive epithelial sodium channel (ENaC) plays a prominent role in sodium uptake from alveolar fluid and is the major component in alveolar fluid clearance in normal and diseased lungs. The lectin-like domain of TNF-α has been shown to activate amiloride-sensitive sodium uptake in type II alveolar epithelial cells. Therefore, several synthetic peptides that mimic the lectin-like domain of TNF-α (TIP) were synthesized and their ability to enhance sodium current through ENaC was st  ...[more]

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