Phenotypic characterisation of the sodium hydrogen exchanger and NADPH oxidase enzyme in pre-eclampsia
thesisposted on 2014-12-15, 10:30 authored by Virginia. Lee
Although the underlying aetiology of pre-eclampsia remains an enigma, it is only recently that oxidative stress and membrane transport abnormalities associated with sodium have been implicated. These represent two factors that may constitute the pre eclamptic phenotype proving important in the pathogenesis of the disease. White cell Na+/H+ exchanger activity was increased in pre-eclamptic pregnancy with respect to normotensive pregnant controls and persisted into the post-partum period. This was not due to increased expression of a 97kDa NHE-1 protein but possibly genetically determined due to the persistence of the phenotype in transformed lymphoblasts. Cells isolated from pre-eclamptic women exhibited an intracellular acidosis that again, persisted into the post-partum period. The mechanism(s) responsible were unclear but may have been associated with inhibition of the Na+K+ATPase by a digoxin-like factor. Neutrophil NADPH oxidase mediated reactive oxygen species production was measured using a chemiluminescent technique. These results were affected by the intracellular acidosis consequently measurements were performed in Epstein-Barr virus immortalized lymphoblasts. Upregulated NADPH oxidase activity was identified in pre-eclamptic and post-partum pre-eclamptic cells with tyrosine kinase signal transduction pathways being implicated in their control. Enhanced activity may have been influenced by a genetically determined phenotype resulting in an increased sensitivity of the enzyme. Collectively, this data adds to our understanding of pre-eclampsia and provides phenotypic characterisation of the Na+/H+ exchanger and NADPH oxidase enzyme. These membrane functions may have implications as markers for predisposition to disease or in therapeutic intervention.
Date of award2002-01-01
Awarding institutionUniversity of Leicester