Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.495039
Title: Pregnane X receptor and primary biliary cirrhosis
Author: Konstantinou, Dimitrios
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2008
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Abstract:
This thesis showed that there is overlap between the PXR and a related nuclear receptor termed the constitutive androstane receptor (CAR). The murine pyruvate dehydrogenase complex E2 (PDC-E2) was cloned, expressed, purified and used as antigen for ELISA experiments. Next, three annual studies were carried out in SJL/J mice, by sensitising them with a PDC-E2 derived peptide (p163), in order to check if these mice develop cholangiopathy. Then, two animal studies were carried out in order to check the effect of pregnenolone-16alpha-carbonitrile (PCN) in PXR-/- and PXR +/+(C57BL6 background) mice chronically treated with carbon tetrachloride (CCI4). The result was that PCN did not inhibit the hepatotoxicity of CCI4. Furthermore, a mouse line was derived that could be susceptible to the development of cholangiopathy (SJL/J- PXR-/- ) and wild type (SJL/J- PXR+/+) control. Immunisation of SJL/J- PXR-/- and SJL/J-PXR+/+ with p163 peptide increased the portal tract inflammation equally in mice over CFA control. Treating these mice with lithocholic acid (LCA) produced a higher level of portal tract inflammation in knockout mice than in wild type. Moreover, twelve Single Nucleotide Polymorphisms (SNPs), on human PXR gene, were studied in relation to lipid profile in Glasgow population (P-population). Interestingly, two of them (PXR3 and PXR8) had strong association with lipoprotein variations especially in the male population. Three SNPs (PXR1, PXR2 and PXR8) on human PXR gene were studied between PBC samples and control groups and the results showed that these three genetic variations did not particularly predispose to the disease. Finally one polymorphism (PXR11) on human PXR gene was studied between hyperlipidemia and control group but again our results showed that this specific SNP did not predispose to hyperlipidemia.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.495039  DOI: Not available
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