S-glutathionylation of the Na+-K+ Pump: A Novel Redox Mechanism in Preeclampsia

Abstract

Abstract 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 β 1 subunit (GSS-β 1) protein glutathionylation of the Na+-K + pump occurs in preeclampsia. Methods The GSS-β1 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-β 1 of the Na+-K+ pump, compared to healthy pregnancies (n = 11, mean gestational age 39 weeks). The potential pathogenetic role of GSS-β 1-mediated Na+-K+ pump dysfunction in preeclampsia was investigated. Results Protein expression of the β 1 subunit was unchanged in placentas from women with preeclampsia vs those with normotensive pregnancies. Preeclamptic placentas had a significantly increased GSS-β 1 of the Na+-K+ pump compared to those from healthy pregnancies, and this was linked to a decrease in α 1/β 1 subunit coimmunoprecipitation. The cytosolic p47phox nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase subunit and its coimmunoprecipitation with the α 1 Na+-K+ pump subunit was increased in preeclamptic placentas, thus implicating NADPH oxidase–dependent pump inhibition. Conclusions The high level of β 1 pump subunit glutathionylation provides new insights into the mechanism of Na+-K+ pump dysfunction in preeclampsia.