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The expression of prion protein in the vasculature

Starke, Richard David; (2003) The expression of prion protein in the vasculature. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

The aim of my thesis was to study the expression of prion protein (PrPC) in the vasculature. The function of PrPC is unknown but it is thought to refold into a pathogenic form termed PrPSC which damages neurones in the brain causing transmissible spongiform encephalopathies. I studied the expression of PrPC in CD34 positive stem cells, reticulocytes, erythrocytes and megakaryocytes. These cells were found to be positive for PrPC with a general trend for increased expression during megakaryocyte maturation and a decrease in expression during erythropoiesis. Since megakaryocytes were positive for PrPC I hypothesised that they were the source of platelet PrPC. I studied the expression, location and function of PrPC in platelets. PrPC was found in platelet alpha-granules and was transported to the cell surface upon cellular activation. Crosslinking PrPC on the platelet surface was found to be associated with signal transduction phosphorylation events, but there was no apparent increase in platelet function. I hypothesised that the origin of blood plasma PrPC was the vascular endothelium. Microvascular and macrovascular endothelial cells were found to express and release soluble PrPC in a constitutive manner with no increase in expression upon cellular activation. Measurement of plasma PrPC levels in patients with varying blood cell counts demonstrated no association between platelet, erythrocyte or leucocyte counts and the PrPC concentration. Patients with a variety of chronic vascular diseases had a normal PrPC concentration in their blood plasma. However there was a higher level of PrPC in plasma from patients with renal failure that was not removed by renal dialysis. In summary I have provided a detailed analysis of the expression of PrPC in several cells of the vasculature for the first time. Although its function is unclear PrPC must be of significant importance for such a large and widespread distribution.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: The expression of prion protein in the vasculature
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Prion proteins
URI: https://discovery.ucl.ac.uk/id/eprint/10102642
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