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Title: Oxygen radical generation by lymphoblast NADPH oxidase in hypertension
Author: Pettit, Andrew I.
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2006
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Objectives. The aim of this thesis was to investigate increased reactive oxygen species production originating from NADPH oxidase in lymphoblasts from hypertensive subjects. Results. Combined intra and extracellular stimulated reactive oxygen species production was increased in hypertensive cell lines. The ROS production was abolished by Diphenyleneiodonium chloride but not by rotenone, indicating that a non-mitochondrial flavoprotein, such as NADPH oxidase, was involved. Analysis of NADPH oxidase subcomponents revealed an increase in p22phox in lymphoblasts from hypertensive subjects, accounting for some of the increased reactive oxygen species production. There was increased basal Tyr/Thr phosphorylation of p44/p42 MAPK in the hypertensive lymphoblasts, but the difference was lost on stimulation. The various kinase inhibitors had no effect on basal reactive oxygen species production. Tyrosine kinase inhibition produced up to 70% reduction in stimulated reactive oxygen species production in both cell lines. Inhibition of p44/p42 MAPK kinase, P13K, and PLA2 produced a small reduction in stimulated ROS production. There was no differential reduction in ROS production from the hypertensive group with these inhibitors, suggesting no role of these pathways in priming of NADPH oxidase. Conclusions. We have shown there is increased reactive oxygen species production in lymphoblasts from hypertensive subjects probably originating from NADPH oxidase. Increased expression of p22phox in hypertension lymphoblasts accounts for approximately a third of the increased reactive oxygen species production. We could not demonstrate tyrosine kinase, p38 MAPK, p44/p42 MAPK, P13K or PLA2 priming of reactive oxygen species production.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available