Different neuronal Na(+)/K(+)-ATPase isoforms are involved in diverse signaling pathways.
Inhibition of rat neuronal Na(+)/K(+)-ATPase alpha3 isoform at low (100 nM) ouabain concentration led to activation of MAP kinase cascade via PKC and PIP(3) kinase. In contrast to ouabain-sensitive alpha3 isoform of Na(+)/K(+)-ATPase, an ouabain-resistant alpha1 isoform (inhibition with 1 mM of ouabain) of Na(+)/K(+)-ATPase regulates MAP kinase via Src kinase dependent reactions. Using of Annexin V-FITC apoptotic test to determine the cells with early apoptotic features allows to conclude that alpha3 isoform stimulates and alpha1 suppresses apoptotic process in cerebellum neurons. These data are the first demonstration showing participation of ouabain-resistant (alpha1) and ouabain-sensitive (alpha3) Na(+)/K(+)-ATPase isoforms in diverse signaling pathways in neuronal cells.
Karpova
Larisa V
LV
Department of Biochemistry, M.V. Lomonosov Moscow State University, Moscow, Russia. karpovalarisa@gmail.com
Bulygina
Elena R
ER
Boldyrev
Alexander A
AA
D000818:Animals; D017209:Apoptosis; D002531:Cerebellum / Q000166:cytology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009474:Neurons / Q000201:enzymology*; D010042:Ouabain / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010042:Ouabain; D019869:Phosphatidylinositol 3-Kinases; D020033:Protein Isoforms; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase; D019061:src-Family Kinases