| Autor: |
Liu, Lian, Duke, Billie Jeanne, Malik, Bela, Yue, Qiang, Eaton, Douglas C. |
| Předmět: |
|
| Zdroj: |
American Journal of Physiology: Renal Physiology; Jun2009, Vol. 296 Issue 6, pF1417-F1427, 11p, 13 Graphs |
| Abstrakt: |
The epithelial sodium channel (ENaC) is regulated by epidermal growth factor (EGF). We investigate whether ENaC is regulated by another EGF receptor (EGFR) ligand, transforming growth factor-α (TGF-α). We show that chronic (24 h) treatment with TGF-α inhibits ENaC in Xenopus laevis kidney cells 20 times more strongly than EGF. By using single-channel measurements, we show that TGF-α significantly reduces the number of ENaC per patch. The open probability (Po) is unchanged by 24-h treatment with TGF-α. α-, β-, and γ-ENaC mRNA levels are significantly reduced by TGF-α or EGF. TGF-α or EGF reduces α- and γ-ENaC proteins in the membrane; however, β-ENaC is unchanged. TGF-α or EGF inhibits ENaC by activating EGFR since the EGFR inhibitor AG 1478 blocks the effects of both. The MAPK 1/2 inhibitor U0126 also blocks the effect of TGF-α or EGF on ENaC, indicating that the MAPKI/2 pathway is involved in the TGF-α- or EGF-induced inhibition of ENaC. Interestingly, acute treatment (o. Pretreatment of the cells with U0126 potentiates the acute TGF-α- or EGF-induced stimulation of ENaC. This TGF-α- or EGF-induced increase in sodium current is abolished by a phosphatidylinositol 3-kinase (P1-3 kinase) inhibitor, LY294002, suggesting that P1-3 kinase is involved in the activation of sodium transport. In conclusion, chronic treatment with TGF-α or EGF inhibits ENaC by decreasing the number of channels in the membrane transcriptionally through MAPK1/2 pathways, but acute treatment with TGF-α or EGF activates ENaC by increasing Po via PI-3 kinase. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
