Inhibition of Na,K-ATPase activates PI3 kinase and inhibits apoptosis in LLC-PK1 cells
| Autor: | Tzvetanka Bondeva, Guisen Jiang, Aiping Zhao, Xiaoming Zhou, Tamas Balla, Przemyslaw Hirszel |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Swine
Biophysics Apoptosis Biology Protein Serine-Threonine Kinases Biochemistry Ouabain Wortmannin chemistry.chemical_compound Phosphatidylinositol 3-Kinases Proto-Oncogene Proteins medicine Animals LY294002 Kinase activity Na+/K+-ATPase Enzyme Inhibitors Phosphorylation Molecular Biology Protein kinase B urogenital system Kinase Cell Biology Molecular biology Cell biology Culture Media Enzyme Activation chemistry Dactinomycin LLC-PK1 Cells Sodium-Potassium-Exchanging ATPase Proto-Oncogene Proteins c-akt medicine.drug |
| Zdroj: | Biochemical and biophysical research communications. 285(1) |
| ISSN: | 0006-291X |
| Popis: | In the present study we used LLC-PK1 cells, a porcine renal proximal tubular cell line, to investigate whether PI3 kinase activation was involved in the anti-apoptotic effect of ouabain, a specific inhibitor of Na,K-ATPase. Apoptosis was induced by actinomycin D (Act D, 5 microM) and assessed by appearance of hypodiploid nuclei and DNA fragmentation. Ouabain attenuated Act D-induced apoptotic response in a dose-dependent manner. Incubation in a low K(+) medium (0.1 mM) which is another way to decrease Na,K-ATPase activity also had anti-apoptotic effect. Both ouabain and low K(+) medium increased the PI3 kinase activity in p85 immunoprecipitates. Ouabain, as well as incubation in the low K(+) medium, also increased the phosphorylation of Akt. Inhibition of PI3 kinase by either wortmannin or LY294002 reversed the cytoprotective effect of ouabain. These data together indicate that inhibition of Na,K-ATPase activates PI3 kinase in LLC-PK1 cells which could then exert the cytoprotective effect. |
| Databáze: | OpenAIRE |
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