| Autor: |
Woollhead, Alison M., Scott, John W., Albert, Anthony P., Kalsi, Kameljit K., Hardie, D. Grahame, Baines, Deborah L. |
| Předmět: |
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| Zdroj: |
FASEB Journal; Apr2007, Vol. 21 Issue 6, pA954-A954, 1/5p |
| Abstrakt: |
We have previously shown that phenformin and the AMP mimetic drug AICAR decreased transepithelial amiloride-sensitive Na+ transport (Iamiloride), apical Na+ conductance (GNa+) and ouabain-sensitive Na+K+ATPase (Iouabain) activity in H441 lung epithelial cells. We have further explored the effect of these drugs on cellular AMP:ATP ratio, the activation of AMP activated protein kinase (AMPK) and Na+ transport across H441 cells via the epithelial Na+ channel ENaC. The cellular AMP:ATP ratio was increased 3 fold compared to control after treatment with phenformin (5mM) but did not change with AICAR (2mM). Both drugs induced a ∼2.0 fold increase in AMPK activity from 0.03±0.002 to 0.05±0.008 and 0.04±0.004 to 0.07±0.005 nmols/min/mg respectively. Phenformin and AICAR inhibited transepithelial Iamiloride but the effect of phenformin was not reversed by the AMPK kinase inhibitor Compound C (80µM). In contrast to AICAR, phenformin induced a rapid decrease in constitutive activity of a 6.09±0.94 pS amiloride-sensitive channel which correlated with increased association of Nedd4-2 with α and γENaC proteins but not changes in ENaC protein abundance via increased retrieval of ENaC proteins from the membrane. These data indicate that phenformin and AICAR decrease Iamiloride through different mechanisms. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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