University of Groningen In vitro studies on the cytoprotective properties of Carbon monoxide releasing molecules and N-acyl dopamine derivatives Stamellou, Eleni IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2016 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Stamellou, E. (2016). In vitro studies on the cytoprotective properties of Carbon monoxide releasing molecules and N-acyl dopamine derivatives [Groningen]: University of Groningen Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 09-04-2018
In vitro studies on the cytoprotective properties of Carbon monoxide releasing molecules and N-acyl dopamine derivatives Eleni Stamellou 2016 1
This Ph.D. thesis was supported by: Hochschule Mannheim, Germany Medical Faculty Mannheim, Heidelberg University, Germany Groningen Institute for Drug Exploration (GUIDE) University Medical Center Groningen, University of Groningen, The Netherlands Printing of this thesis was financially supported by: University Medical Center Groningen, University of Groningen, The Netherlands Cover design and layout: Eleni Stamellou Printed: Unicopy, Aachen, Germany @ Copyright 2016 by Eleni Stamellou All rights reserved. No part of this publication may be reproduced or transmitted any form or any means without permission of the author. ISBN (printed): 978-90-367-8661-4 ISBN (digital): 978-90-367-8660-7 2
In vitro studies on the cytoprotective properties of Carbon monoxide releasing molecules and N-acyl dopamine derivatives PhD thesis to obtain the degree of PhD at the University of Groningen On the authority of the Rector Magnificus Prof. E. Sterken and in accordance with the decision by the College of Deans. This Thesis will be defended in public on Wednesday 2 March 2016 at 12:45 by Eleni Stamellou born on 14 th September, 1984 in Athens, Greece 3
Promoters: Prof. Dr. Willem J van Son Prof. Dr. Benito A. Yard Copromoters: Prof. Dr. Mathias Hafner Dr. Marc Seelen Assessment committee: Prof. Dr. H-P. Hammes Prof. Dr. Rob Henning Prof. Dr. Tammo Ostendorf 4
Paranimfen: Prama Pallavi Anna-Maria Bellou 5
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Contents CHAPTER 1... 11 General Introduction and aim of the Thesis... 12 CHAPTER 2... 21 Carbon monoxide: Friend and Foe... 21 CHAPTER 3... 28 N-acyl dopamine derivatives as lead compound for implementation in transplantation medicine.... 29 CHAPTER 4... 41 Enzyme-triggered CO-Releasing Molecules (ET-CORMs): evaluation of biological activity in relation to their structure... 41 CHAPTER 5... 67 a. Acyloxy-diene-Fe(CO) 3 Complexes with variable chain lengths... 77 b. Iron Dienylphosphate Tricarbonyl Complexes... 83 CHAPTER 6... 89 Different design of Enzyme-triggered CO-releasing molecules (ET-CORMs) reveals quantitative differences in biological activities in terms of toxicity and inflammation.... 89 CHAPTER 7... 113 N-octanoyl dopamine transiently inhibits T cell proliferation via G1 cell cycle arrest and inhibition of redox dependent transcription factors... 113 CHAPTER 8... 137 N-octanoyl dopamine treatment of endothelial cells induces the unfolded protein response and results in hypometabolism and tolerance to hypothermia... 137 CHAPTER 9... 163 Analyses of different synthetic N-acyl dopamine derivatives reveal different structural requirements for their anti-inflammatory effect and TRPV1 activation... 163 Chapter 10... 187 7
Summary... 188 Conclusion and future perspectives... 193 APPENDIX... 197 Author affiliations... 198 Acknowledgements... 201 Publication List... 203 References... 205 8
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