Queen's University - Utility Bar

QSpace at Queen's University >
Graduate Theses, Dissertations and Projects >
Queen's Graduate Theses and Dissertations >

Please use this identifier to cite or link to this item: http://hdl.handle.net/1974/5173

Title: The Role of Compartmented cAMP Signalling in the Regulation of Vascular Endothelial Cell Permeability
Authors: Rampersad, Sarah

Files in This Item:

File Description SizeFormat
Rampersad_Sarah_N_200909_MSc.pdf5.28 MBAdobe PDFView/Open
Keywords: barrier function
phosphodiesterase 4D
vascular endothelial cells
Issue Date: 2009
Series/Report no.: Canadian theses
Abstract: Vascular endothelial cells (VECs) maintain vascular integrity by regulating the passage of solutes, macromolecules, and cells between the vascular and perivascular space and are critical in a wide number of physiological processes, such as the delivery of nutrients and oxygen to surrounding tissues, leukocyte trafficking, angiogenesis, and tissue repair. VEC permeability is regulated, at least in part, by VE-cadherin-based adherens junctions that coordinate inter-VEC contacts and communicate the strength of these interactions to the cell via the actin cytoskeleton. Although the ubiquitous second messenger, cyclic adenosine 3'€™, 5'€™-monophosphate (cAMP), has been shown to reduce VEC permeability, the molecular basis of this effect is currently unclear. Herein, we report that cAMP and its two effectors, cAMP-dependent protein kinase A-II (PKA-II) and exchange protein activated by cAMP-1 (EPAC1), improve barrier function and differentially coordinate this effect through both VE-cadherin and actin cytoskeletal structures. We have also identified cyclic nucleotide phosphodiesterase (PDE) 4 as the major PDE regulating VEC barrier function. Through the use of cAMP-elevating agents and RNAi-mediated knockdown of PKA-Cα, EPAC1 and PDE4D, we have identified a dominant role for EPAC1 in VEC permeability as well as recognized PDE4D as a potential adaptor protein VE-cadherin-based complexes. Our results are consistent with previous reports of a role for both PKA and EPAC1 in controlling VE-cadherin mediated barrier function and additionally provide novel insight into the differential roles that PKA, EPAC1 and PDE4D play in stabilizing VEC barrier function.
Description: Thesis (Master, Pathology & Molecular Medicine) -- Queen's University, 2009-09-18 16:09:59.12
URI: http://hdl.handle.net/1974/5173
Appears in Collections:Queen's Graduate Theses and Dissertations
Department of Pathology and Molecular Medicine Graduate Theses

Items in QSpace are protected by copyright, with all rights reserved, unless otherwise indicated.


  DSpace Software Copyright © 2002-2008  The DSpace Foundation - TOP