Matches in SemOpenAlex for { <https://semopenalex.org/work/W2942541247> ?p ?o ?g. }
Showing items 1 to 75 of
75
with 100 items per page.
- W2942541247 abstract "The inner lining of the vasculature is a monolayer of endothelial cells that performs a multitude of functions with importance for cardiovascular health.Many of the functions are regulated by or are dependent on the calcium ion (Ca2+), a major intracellular signalling factor.The overall aim of this thesis was to investigate molecular mechanisms and pharmacology of Ca2+ entry mechanisms and their downstream signalling in endothelial cells. Molecular, biochemical and electrophysiology techniques andcell functional assays were used to address two main objectives. The first objective was to investigate putative Ca2+ channel regulator proteins, CRACR2A and golli-MBP. Based on previous reported studies, it was hypothesised that both of these proteins would have a role in regulatingendothelial cell store-operated Ca2+ entry. However, unexpectedly these proteins had Ca2+ channel-independent functions, leading to alternative hypotheses about their roles in endothelial cells. The second objective was togenerate new information about pharmacology targeted to a Ca2+ channel subunit, TRPC6, which has been suggested to be important in endothelial cell biology. Specifically, it was hypothesised that the anti-cancer agent carboxyamidotriazole (CAI) and the flavanol galangin and its derivatives, which have previously been shown to inhibit intracellular Ca2+, were TRPC6 channelinhibitors.Endothelial cells did not express CRACR2A as reported for T cells (Srikanth et al., 2010) but did express a longer splice variant arising from the same gene, EFCAB4B isoform a (EFCAB4B-a). CRACR2A and EFCAB4B-a have the sameputative Ca2+ binding domains at their N termini but EFCAB4B-a, unlike CRACR2A, had no role in the regulation of Ca2+ release-activated Ca2+ (CRAC) channels. Instead, EFCAB4B-a contained a predicted Rab domain in its Cterminus and was therefore a putative monomeric G protein. It localised to endothelial cell specific Weibel-Palade bodies and influenced the abundance of the pro-thrombotic agent von Willebrand factor. Golli-MBP was found expressed in endothelial cells but again there was little effect on CRAC channel activity. Instead golli-MBP was identified as a positive regulator of the important endothelial growth factor receptor, VEGFR2. The small-molecule CAI, was identified as an inhibitor of TRPC6 channelswithout effect on TRPC5 or TRPV4 channels. A range of flavonol compounds was also identified as TRPC6 inhibitors.In summary, this research has generated new information and hypotheses about a putative Ca2+-regulated Rab protein of Weibel-Palade bodies, a novel regulator of a key endothelial growth factor receptor, and a molecular target for CAI. It has, therefore, led to understanding of molecular mechanisms and pharmacology in endothelial cells which may be useful for devising strategies to treat life-threatening conditions such as cardiovascular disease and cancer." @default.
- W2942541247 created "2019-05-09" @default.
- W2942541247 creator A5073148223 @default.
- W2942541247 date "2013-09-01" @default.
- W2942541247 modified "2023-09-24" @default.
- W2942541247 title "Regulation of endothelial calcium-dependent phenomena by calcium-regulated proteins" @default.
- W2942541247 hasPublicationYear "2013" @default.
- W2942541247 type Work @default.
- W2942541247 sameAs 2942541247 @default.
- W2942541247 citedByCount "0" @default.
- W2942541247 crossrefType "dissertation" @default.
- W2942541247 hasAuthorship W2942541247A5073148223 @default.
- W2942541247 hasConcept C123012128 @default.
- W2942541247 hasConcept C128448793 @default.
- W2942541247 hasConcept C155164980 @default.
- W2942541247 hasConcept C158617107 @default.
- W2942541247 hasConcept C162740809 @default.
- W2942541247 hasConcept C170493617 @default.
- W2942541247 hasConcept C178790620 @default.
- W2942541247 hasConcept C181080969 @default.
- W2942541247 hasConcept C185592680 @default.
- W2942541247 hasConcept C18699975 @default.
- W2942541247 hasConcept C201571599 @default.
- W2942541247 hasConcept C202751555 @default.
- W2942541247 hasConcept C2776610495 @default.
- W2942541247 hasConcept C519063684 @default.
- W2942541247 hasConcept C55493867 @default.
- W2942541247 hasConcept C79879829 @default.
- W2942541247 hasConcept C86803240 @default.
- W2942541247 hasConcept C95444343 @default.
- W2942541247 hasConceptScore W2942541247C123012128 @default.
- W2942541247 hasConceptScore W2942541247C128448793 @default.
- W2942541247 hasConceptScore W2942541247C155164980 @default.
- W2942541247 hasConceptScore W2942541247C158617107 @default.
- W2942541247 hasConceptScore W2942541247C162740809 @default.
- W2942541247 hasConceptScore W2942541247C170493617 @default.
- W2942541247 hasConceptScore W2942541247C178790620 @default.
- W2942541247 hasConceptScore W2942541247C181080969 @default.
- W2942541247 hasConceptScore W2942541247C185592680 @default.
- W2942541247 hasConceptScore W2942541247C18699975 @default.
- W2942541247 hasConceptScore W2942541247C201571599 @default.
- W2942541247 hasConceptScore W2942541247C202751555 @default.
- W2942541247 hasConceptScore W2942541247C2776610495 @default.
- W2942541247 hasConceptScore W2942541247C519063684 @default.
- W2942541247 hasConceptScore W2942541247C55493867 @default.
- W2942541247 hasConceptScore W2942541247C79879829 @default.
- W2942541247 hasConceptScore W2942541247C86803240 @default.
- W2942541247 hasConceptScore W2942541247C95444343 @default.
- W2942541247 hasLocation W29425412471 @default.
- W2942541247 hasOpenAccess W2942541247 @default.
- W2942541247 hasPrimaryLocation W29425412471 @default.
- W2942541247 hasRelatedWork W1971480095 @default.
- W2942541247 hasRelatedWork W1973950863 @default.
- W2942541247 hasRelatedWork W1976372232 @default.
- W2942541247 hasRelatedWork W2013509592 @default.
- W2942541247 hasRelatedWork W2024940074 @default.
- W2942541247 hasRelatedWork W2029511829 @default.
- W2942541247 hasRelatedWork W2030169966 @default.
- W2942541247 hasRelatedWork W2032234475 @default.
- W2942541247 hasRelatedWork W2049242498 @default.
- W2942541247 hasRelatedWork W2053758521 @default.
- W2942541247 hasRelatedWork W2074134623 @default.
- W2942541247 hasRelatedWork W2117472172 @default.
- W2942541247 hasRelatedWork W2143547356 @default.
- W2942541247 hasRelatedWork W2216872319 @default.
- W2942541247 hasRelatedWork W28685655 @default.
- W2942541247 hasRelatedWork W2942151678 @default.
- W2942541247 hasRelatedWork W2967845993 @default.
- W2942541247 hasRelatedWork W3023647903 @default.
- W2942541247 hasRelatedWork W46610168 @default.
- W2942541247 hasRelatedWork W2517258150 @default.
- W2942541247 isParatext "false" @default.
- W2942541247 isRetracted "false" @default.
- W2942541247 magId "2942541247" @default.
- W2942541247 workType "dissertation" @default.