Cardiac glycoside ouabain induces activation of ATF-1 and StAR expression by interacting with the α4 isoform of the sodium pump in Sertoli cells.

摘要: Sertoli cells express α1 and α4 isoforms of the catalytic subunit Na(+),K(+)-ATPase (sodium pump). Our recent findings demonstrated that interactions isoform with cardiotonic steroids (CTS) like ouabain induce signaling cascades resemble so-called non-classical testosterone pathway characterized by activation c-Src/c-Raf/Erk1/2/CREB cascade. Here we investigate a possible physiological significance activated The results obtained in current investigation show ouabain-induced cascade also leads to CREB-related activating transcription factor 1 (ATF-1) cell line 93RS2 concentration- time-dependent manner, as detection ATF-1 phosphorylated on Ser63 western blots. ouabain-activated protein was found localize nuclei. sodium pump mediates this activation, it is ablated when are incubated siRNA isoform. Ouabain increased expression steroidogenic acute regulator (StAR) protein, which has been shown be downstream consequence CREB/ATF-1 activation. Taking into consideration CTS most likely produced endogenously, induction StAR establishes link between CTS, pump, steroidogenesis crucial for male fertility reproduction.