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Title: Selenoprotein function and expression in human endothelium
Author: Miller, Susan Mary
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2000
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In this thesis the selenoproteins expressed by endothelial cells (isolated from various vascular beds and different species) and the modification of their expression through changes in Se supply and activation of second messenger pathways were studied. The ability of sodium selenite and selenomethionine supplementation to prevent oxidative damage in cultured endothelial cells was also examined, as well as the effect of sodium selenite in stabilising nitric oxide. The present study has confirmed the expression of cytoplasmic glutathione peroxidase (cyGPX) and phospholipid hydroperoxide glutathione peroxidase (PHGPX) in human umbilical vein endothelial cells (HUVEC), however thioredoxin reductase (TR) was found to be the predominant selenoprotein expressed accounting for approximately 43% of the total intracellular 75Se-labelled proteins. No extracellular selenoproteins were synthesised by HUVEC. The overall pattern of selenoprotein expression in endothelial cells isolated from different species and from various human tissue showed considerable variation, though differences were less pronounced when comparing the endothelial cells isolated from various human vascular beds and the human endothelial cell line EAhy926. The expression of TR, cyGPX and PHGPX and other unidentified selenoproteins in HUVEC was significantly modified in response to the phorbol ester phorbol-12-myristate 13-acetate (PMA). A 48 hr incubation with PMA led to significantly decreased expression of both TR and PHGPX (approximately half of that found in untreated cells). Whilst the expression of cyGPX was increased approximately two-fold by PMA treatment, a brief exposure to PMA (one minute) produced similar effects on the expression of these selenoproteins, after a 48 hr lag-period. These effects of PMA could be attenuated by the protein kinase C inhibitor, GF109203X. The calcium ionophore A23187 also modified selenoprotein expression, however time cells began to detach. These observations suggest that the A23187 effect may result from toxicity rather than activation of the calcium signalling pathway.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available