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

Parastoo Hazemi, Susan J. Tzotzos, Bernhard Fischer, Gowri Shankar Bagavananthem Andavan, Hendrik Fischer, Helmut Pietschmann, Rudolf Lucas, Rosa Lemmens-Gruber

Research output: Contribution to journalArticle

17 Scopus citations

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-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 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.

Original languageEnglish (US)
Pages (from-to)8021-8029
Number of pages9
JournalJournal of Medicinal Chemistry
Volume53
Issue number22
DOIs
StatePublished - Nov 25 2010

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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