Essential structural features of TNF-α lectin-like domain derived peptides for activation of amiloride-sensitive sodium current in A549 cells.
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.
Hazemi
Parastoo
P
Department of Pharmacology and Toxicology, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria.
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
D000584:Amiloride / Q000494:pharmacology; D002414:Cations, Monovalent; D045744:Cell Line, Tumor; D062708:Epithelial Sodium Channel Agonists; D053503:Epithelial Sodium Channels / Q000502:physiology; D006801:Humans; D037102:Lectins / Q000737:chemistry*; D008958:Models, Molecular; D018408:Patch-Clamp Techniques; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D057786:Peptidomimetics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012964:Sodium / Q000378:metabolism; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry*
D002414:Cations, Monovalent; D062708:Epithelial Sodium Channel Agonists; D053503:Epithelial Sodium Channels; D037102:Lectins; D010456:Peptides, Cyclic; D057786:Peptidomimetics; D014409:Tumor Necrosis Factor-alpha; D000584:Amiloride; D012964:Sodium; D011188:Potassium