Please use this identifier to cite or link to this item:
|Title: ||Mechanisms and Biological Consequences of Damage to Extracellular Matrix Proteins by Peroxynitrite|
|Authors: ||Degendorfer, Georg|
|Issue Date: ||31-Aug-2015|
|Publisher: ||University of Sydney|
Sydney Medical School
|Abstract: ||Peroxynitrite (ONOO–) is a potent oxidizing and nitrating agent, formed under inflammatory conditions by the diffusion-controlled reaction of superoxide radicals (O2•–) with nitric oxide (•NO). This species reacts rapidly, via both non-radical and radical reactions, with proteins resulting in protein damage. As there are limited antioxidant and repair enzymes extracellularly, damage to extracellular matrix (ECM) proteins is likely to persist and accumulate over time. However, there is a lack of detailed mechanistic information on how ONOO– oxidation and nitration affects ECM proteins. This Thesis investigates the significance of these reactions and how this modulates the structure and function of three different isolated ECM proteins, laminin-111, plasma fibronectin, recombinant tropoelastin and a complex mixture of basement membrane proteins. Exposure of ECM proteins to ONOO– at physiological relevant concentrations (10 μM) lead to protein aggregation and fragmentation. Significant amounts of nitration products (3-nitroTyr, 6-nitroTrp) in the millimolar-range and depletion of corresponding parent Tyr and Trp were detected on all analysed ECM proteins with this effect being modulated by CO2. Furthermore biological function and activity was compromised post ONOO– exposure. Overall, the studies presented in this Thesis provide new information about the reactivity of ONOO– with ECM proteins, and how this affects the structure and the function of these proteins.|
|Access Level: ||Access is restricted to staff and students of the University of Sydney . UniKey credentials are required. Non university access may be obtained by visiting the University of Sydney Library.|
|Rights and Permissions: ||The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.|
|Type of Work: ||PhD Doctorate|
|Type of Publication: ||Doctor of Philosophy Ph.D.|
|Appears in Collections:||Sydney Digital Theses (University of Sydney Access only)|
This work is protected by Copyright. All rights reserved. Access to this work is provided for the purposes of personal research and study. Except where permitted under the Copyright Act 1968, this work must not be copied or communicated to others without the express permission of the copyright owner. Use the persistent URI in this record to enable others to access this work.
|DEGENDORFER Georg - Final Thesis.pdf||Thesis||14.38 MB||Adobe PDF|
Items in Sydney eScholarship Repository are protected by copyright, with all rights reserved, unless otherwise indicated.