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

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• 作者：Parastoo Hazemi ; Susan J. Tzotzos ; Bernhard Fischer ; Gowri Shankar Bagavananthem Andavan ; Hendrik Fischer ; Helmut Pietschmann ; Rudolf Lucas ; Rosa Lemmens-Gruber
• 刊名：Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：November 25, 2010
• 年：2010
• 卷：53
• 期：22
• 页码：8021-8029
• 全文大小：940K
• 年卷期：v.53,no.22(November 25, 2010)
• ISSN：1520-4804

文摘

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.