S-glutathionylation of the Na+-K+ Pump: A Novel Redox Mechanism in Preeclampsia
| Autor: | Annemarie Hennessy, Helge H. Rasmussen, Chia-Chi Liu, Angela Makris, YunJia Zhang |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
medicine.medical_specialty Placenta Endocrinology Diabetes and Metabolism Protein subunit Clinical Biochemistry Context (language use) Oxidative phosphorylation Protein glutathionylation Biochemistry Preeclampsia chemistry.chemical_compound Endocrinology Pre-Eclampsia Pregnancy Internal medicine medicine Humans Na+/K+-ATPase NADPH oxidase biology Biochemistry (medical) Australia medicine.disease Glutathione Oxidative Stress chemistry Case-Control Studies biology.protein Female Sodium-Potassium-Exchanging ATPase Oxidation-Reduction Protein Processing Post-Translational Nicotinamide adenine dinucleotide phosphate |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 106:e1091-e1100 |
| ISSN: | 1945-7197 0021-972X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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