S-glutathionylation of the Na+-K+ pump : 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 β1 subunit (GSS-β1 ) 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-β1 of the Na+ -K+ pump, compared to healthy pregnancies (n = 11, mean gestational age 39 weeks). The potential pathogenetic role of GSS-β1 -mediated Na+ -K+ pump dysfunction in preeclampsia was investigated. Results: Protein expression of the β1 subunit was unchanged in placentas from women with preeclampsia vs those with normotensive pregnancies. Preeclamptic placentas had a significantly increased GSS-β1 of the Na+ -K+ pump compared to those from healthy pregnancies, and this was linked to a decrease in α1 /β1 subunit coimmunoprecipitation. The cytosolic p47phox nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase subunit and its coimmunoprecipitation with the α1 Na+ -K+ pump subunit was increased in preeclamptic placentas, thus implicating NADPH oxidase–dependent pump inhibition. Conclusions: The high level of β1 pump subunit glutathionylation provides new insights into the mechanism of Na+ -K+ pump dysfunction in preeclampsia.