Essential Structural Features of TNF-alpha Lectin-like Domain Derived Peptides for Activation of Amiloride-Sensitive Sodium Current in A549 Cells

Parastoo Hazemi Gavasaraei, Susan J. Tzotzos, Bernhard Fischer, Gowri Shankar Bagavananthem Andavan, Hendrik Fischer, Helmut Pietschmann, Rudolf Lucas, Rosa Lemmens (Korresp. Autor*in)

    Veröffentlichungen: Beitrag in FachzeitschriftArtikelPeer Reviewed


    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-alpha 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-alpha. (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 I 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 treat neat exists for pulmonary permeability edema. Therefore, novel therapies activating sodium uptake from the alveolar fluid via ENaC could improve clinical outcome.
    Seiten (von - bis)8021-8029
    FachzeitschriftJournal of Medicinal Chemistry
    PublikationsstatusVeröffentlicht - 2010

    ÖFOS 2012

    • 3012 Pharmazie, Pharmakologie, Toxikologie