S-Glutathionylation Of The Na+-K+ Pump Is A Novel Redox Mechanism In Preeclampsia

Context: Reduced Na+-K+ pump activity is widely reported in preeclampsia and may be caused by a reversible oxidative modification that is a novel pathological feature of preeclampsia.Objective: This work aims to determine whether beta(1) subunit (GSS-beta(1)) protein glutathionylation of the Na+-K+ pump occurs in preeclampsia.Methods: The GSS-beta(1) of the Na+-K+ pump and its subunit expression in human placentas were compared between women with healthy pregnancies and women with preeclampsia. Human placental samples of pregnant women with preeclampsia (n = 11, mean gestational age 36.5 weeks) were used to examine the GSS-beta(1) of the Na+-K+ pump, compared to healthy pregnancies (n = 11, mean gestational age 39 weeks). The potential pathogenetic role of GSS-beta(1)-mediated Na+-K+ pump dysfunction in preeclampsia was investigated.Results: Protein expression of the beta(1) subunit was unchanged in placentas from women with preeclampsia vs those with normotensive pregnancies. Preeclamptic placentas had a significantly increased GSS-beta(1) of the Na+-K+ pump compared to those from healthy pregnancies, and this was linked to a decrease in alpha(1)/beta(1) subunit coimmunoprecipitation. The cytosolic p47(phox) nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase subunit and its coimmunoprecipitation with the alpha(1) Na+-K+ pump subunit was increased in preeclamptic placentas, thus implicating NADPH oxidase-dependent pump inhibition.Conclusions: The high level of beta(1) pump subunit glutathionylation provides new insights into the mechanism of Na+-K+ pump dysfunction in preeclampsia.