Inhibition of Na,K-ATPase Activates PI3 Kinase and Inhibits Apoptosis in LLC-PK1 Cells

Hydrogen Sulfide Targets EGFR Cys797/Cys798 Residues to Induce Na+/K+-ATPase Endocytosis and Inhibition in Renal Tubular Epithelial Cells and Increase Sodium Excretion in Chronic Salt-Loaded Rats

“…This is in contrast to ouabain-induced Na + /K + -ATPase endocytosis, in which Akt is not involved (17,18). However, PI3K seems to be required for both H 2 S and ouabain, as PI3K has been shown to mediate ouabain signals during Na + /K + -ATPase endocytosis (17,39) in renal tubular epithelial cells. In the present study, H 2 S also activated PI3K, and treatment with PI3K inhibitors abrogated PI3K phosphorylation and Na + /K + -ATPase endocytosis induced by H 2 S. These data suggested that H 2 S signals were transduced to Akt via PI3K.…”

“…Endogenous ouabain binds to ouabain-binding sites on Na + /K + -ATPase, which consequently activates c-Src, EGFR, and PI3K to generate a Na + /K + -ATPase/c-Src/EGFR/PI3K complex (17,39). This complex recruits AP2 to bind with the a subunit of Na + /K + -ATPase and causes Na + /K + -ATPase endocytosis (37).…”

Cardiac glycosides provide neuroprotection against ischemic stroke: Discovery by a brain slice-based compound screening platform

“…By analogy, inhibition of Na ϩ ͞K ϩ -ATPase in the context of ischemic stroke could lead to a positive outcome: in this case as a ''neurotonic'' providing a neuroprotective͞neuroresuscitative benefit as has been previously observed for kidney cells and neurons in some experimental settings (30)(31)(32)(33)(34). Indeed, neriifolin and other cardiac glycosides were recently found to provide neuroprotection against polyglutamine-mediated cytotoxicity (35).…”

A-769662 activates AMPK β1-containing complexes but induces glucose uptake through a PI3-kinase-dependent pathway in mouse skeletal muscle

“…Unpublished observations from Dr. Alexander Chibalin and coworkers show that A-769662 can inhibit the Na ϩ -K ϩ -ATPase (personal communication). In addition, it has been shown in some (11,21,29,30,50) but not all models (23,24) that inhibition of the Na ϩ -K ϩ -ATPase by ouabain increases PI3-kinase activity, possibly through an association between p85 and the ␣ 1 -subunit of the Na ϩ -K ϩ -ATPase, leading to increased Akt phosphorylation. This effect can be inhibited by wortmannin (30).…”