Department of Biochemistry, M.V. Lomonosov Moscow State University, Moscow, Russia.
Cell Biochem Funct. 2010 Mar;28(2):135-41. doi: 10.1002/cbf.1632.
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.
在低浓度（100 nM）哇巴因的作用下，大鼠神经元 Na(+)/K(+)-ATPase alpha3 同工型的抑制作用会通过 PKC 和 PIP(3)激酶导致 MAP 激酶级联反应的激活。与对哇巴因敏感的 Na(+)/K(+)-ATPase alpha3 同工型不同，Na(+)/K(+)-ATPase 的对哇巴因不敏感的 alpha1 同工型（用 1 mM 哇巴因抑制）通过 Src 激酶依赖的反应调节 MAP 激酶。使用 Annexin V-FITC 凋亡试验来确定具有早期凋亡特征的细胞，可得出结论，alpha3 同工型刺激小脑神经元中的凋亡过程，而 alpha1 同工型抑制该过程。这些数据首次证明了对哇巴因不敏感（alpha1）和对哇巴因敏感（alpha3）的 Na(+)/K(+)-ATPase 同工型在神经元细胞中的不同信号通路中发挥作用。
