Inhibition of Na,K-ATPase activates P13 kinase and inhibits apoptosis in LLC-PK1 cells

Citation
Xm. Zhou et al., Inhibition of Na,K-ATPase activates P13 kinase and inhibits apoptosis in LLC-PK1 cells, BIOC BIOP R, 285(1), 2001, pp. 46-51
Citations number
32
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN journal
0006-291X → ACNP
Volume
285
Issue
1
Year of publication
2001
Pages
46 - 51
Database
ISI
SICI code
0006-291X(20010706)285:1<46:IONAPK>2.0.ZU;2-3
Abstract
In the present study we used LLC-PK1 cells, a porcine renal proximal tubula r cell line, to investigate whether PI3 kinase activation was involved in t he anti-apoptotic effect of ouabain, a specific inhibitor of Na,K-ATPase, A poptosis was induced by actinomycin D (Act D, 5 muM) and assessed by appear ance 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 al so had anti-apoptotic effect. Both ouabain and low K+ medium increased the PI3 kinase activity in p85 immunoprecipitates, Ouabain, as well as incubati on in the low K+ medium, also increased the phosphorylation of Akt, Inhibit ion of PI3 kinase by either wortmannin or LY294002 reversed the cytoprotect ive 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 cy toprotective effect.