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Sodium pump α1 and α3 subunit isoforms mediate distinct responses to ouabain and are both essential for survival of human neuroblastoma
Author(s) -
Karpova Larisa,
Eva Alexander,
Kirch Ulrike,
Boldyrev Alexander,
ScheinerBobis Georgios
Publication year - 2010
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2010.07602.x
Subject(s) - ouabain , protein subunit , gene isoform , neuroblastoma , transfection , extracellular , kinase , small interfering rna , microbiology and biotechnology , biology , chemistry , cell culture , sodium , biochemistry , gene , genetics , organic chemistry
Using SK‐N‐AS human neuroblastoma cells, which co‐express the α1 and α3 isoforms of the sodium pump α subunit, we selectively silenced either the α1 or α3 subunit by means of transfection with small interfering RNA, and investigated cell survival and the cellular response to ouabain. We found that both of the α subunits are essential for cell survival, indicating that substitution of one subunit for the other is not sufficient. In the presence of both α subunits, ouabain causes sustained activation of extracellular signal‐regulated kinases 1 and 2 (Erk1/2). This activation is not affected when the α1 subunit is silenced. However, when α3 expression is silenced, ouabain‐induced activation of Erk1/2 does not occur, even at a high concentration of ouabain (1 μ m ). Thus, ouabain‐induced Erk1/2 activation is mediated in SK‐N‐AS cells by α3 only, and α1 does not participate in this event. This is a clear demonstration of selective involvement of a specific sodium pump α subunit isoform in ouabain‐induced signaling.