Title:Ouabain-Induced Signaling and Cell Survival in SK-N-SH Neuroblastoma Cells Differentiated by Retinoic Acid
Volume: 14
Issue: 10
Author(s): Evgeny E. Akkuratov, Jian Wu, David Sowa, Zahoor A. Shah and Lijun Liu
Affiliation:
Keywords:
Na+/K+-ATPase, neuroblastoma, ouabain, retinoic acid, phosphoinositide 3-kinase, signaling cascades.
Abstract: Ouabain stimulates activation of various signaling cascades such as protein kinase B (Akt)
and Extracellular-signaling-regulated kinase 1/2 (ERK 1/2) in various cell lines. Retinoic acid (RA) is commonly used to
induce neuroblastoma differentiation in cultures. Upon RA administration, human neuroblastoma cell line, SK-N-SH
demonstrated neurite extensions, which is an indicator of neuronal cell differentiation. Here we report that ouabaininduced
signaling is altered under the action of 1 μM RA in human neuroblastoma SK-N-SH cells. RA increased the
expression of p110α subunit of phosphoinositide 3-kinase (PI3K), Akt and β1 subunit of Na+/K+-ATPase. Ouabain
activated Akt and ERK 1/2 in differentiated SK-N-SH cells; this effect was not observed in non-differentiated SK-N-SH
cells. Long-term incubation of non-differentiated SK-N-SH with 1 μM ouabain led to a decrease in the number of cells;
this effect was reduced in differentiated SK-N-SH cells. Taken together, these results suggest that ouabain leads to cell
death in neuroblastoma cells rather than neuronal cells due to the different response to ouabain manifested by activation of
Akt and ERK 1/2.
Highlights
RA increases the expression of p110α subunit of PI3K, Akt and β1 subunit of Na+/K+-ATPase
Ouabain induces activation of Akt and ERK 1/2 in differentiated SK-N-SH cells but not in non-differentiated cells
1 µM ouabain leads to a decrease in the number of cells in non-differentiated SK-N-SH
Reduction of ouabain-induced cell death in differentiated SK-N-SH