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Diseases 2013, 1(1), 1-17; https://doi.org/10.3390/diseases1010001

Protein Kinase C Epsilon Contributes to NADPH Oxidase Activation in a Pre-Eclampsia Lymphoblast Cell Model

Pharmacology and Therapeutics Group, Department of Cardiovascular Sciences, Leicester Royal Infirmary and NIHR Cardiovascular Biomedical Research Unit, Clinical Sciences Building, Leicester, LE2 7LX, UK
Current address: Endocrinology and Diabetes, Institute of Human Development, AV Hill Building University of Manchester, Manchester, M13 9PT, UK.
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Received: 15 July 2013 / Revised: 16 August 2013 / Accepted: 19 August 2013 / Published: 28 August 2013
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Abstract

Pre-eclampsia is a pregnancy-specific disorder characterised by hypertension and proteinuria, which in severe cases results in multi-system disturbances. The maternal syndrome is associated with a pro-inflammatory state, consisting of leukocyte activation, which is thought to contribute to the widespread endothelial dysfunction. We previously showed increased activation of NADPH oxidase in pre-eclampsia, in both neutrophils and B-lymphoblast cell lines (B-LCLs). In this study, the mechanism by which NADPH oxidase activity is increased in pre-eclampsia was further investigated. NADPH oxidase activity was found to be increased in phorbol-12-myristate-13-acetate (PMA) stimulated B-LCLs isolated from women with pre-eclampsia. This correlated with an increase in protein kinase C (PKC) substrate phosphorylation, p47-phox phosphorylation (a regulatory component of NADPH oxidase) and p47-phox directed-kinase activity. Using ion exchange and hydroxyapatite chromatography we identified a major peak of PMA regulated p47-phox kinase activity. Chromatography fractions were probed for PKC isoforms. We found the major peak of p47-phox kinase activity could not be separated from the elution profile of PKC epsilon. Using a peptide inhibitor of PKC epsilon, PMA-induced reactive oxygen species (ROS) production could be reduced to that of a normal B-LCL. These data suggest a pro-inflammatory role for PKC epsilon in the pathogenesis of pre-eclampsia. View Full-Text
Keywords: pre-eclampsia; NADPH oxidase; protein kinase C; free radicals; hypertension pre-eclampsia; NADPH oxidase; protein kinase C; free radicals; hypertension
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Poolman, T.M.; Quinn, P.A.; Ng, L. Protein Kinase C Epsilon Contributes to NADPH Oxidase Activation in a Pre-Eclampsia Lymphoblast Cell Model. Diseases 2013, 1, 1-17.

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