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Permanent link (DOI): https://doi.org/10.7939/R3804XR97

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New insights into epoxyeicosatrienoic acid-mediated protective effects in cardiac cells Open Access

Descriptions

Other title
Subject/Keyword
Autophagy
HL-1 cells
Neonatal Cardiomyocytes
Starvation
epoxyeicosatrienoic acids
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Alsaleh, Nasser B
Supervisor and department
Seubert, John (Pharmacy and Pharmaceutical Sciences)
Examining committee member and department
Siraki, Arno (Pharmacy and Pharmaceutical Sciences)
Dyck, Jason (Department of Pediatrics)
Jurasz, Paul (Pharmacy and Pharmaceutical Sciences)
Department
Faculty of Pharmacy and Pharmaceutical Sciences
Specialization
Pharmaceutical Sciences
Date accepted
2014-03-31T15:16:05Z
Graduation date
2014-06
Degree
Master of Science
Degree level
Master's
Abstract
Epoxyeicosatrienoic acids (EET) are cytochrome P450 epoxygenase metabolites of arachidonic acid. Evidence shows that they mediate protective effects in the cardiovascular system promoting cell survival. In this thesis, the major focus was to investigate if and how EETs regulate autophagy in cardiac cells during starvation. We used a dual-acting synthetic analog, UA-8 (13-(3-propylureido)tridec-8-enoic acid), possessing EET-mimetic and soluble epoxide hydrolase inhibitory properties. Our results demonstrated that UA-8 modulated an autophagic response in starved cells improving cell viability and enhancing recovery. Furthermore, UA-8 reduced both caspase-3 and total proteasome activities. Genetic as well as pharmacological inhibition of autophagy abolished the UA-8-mediated protective effects. Mechanistic studies demonstrated that sarcolemmal ATP-sensitive potassium channels and activation of AMPK are involved in the UA-8-mediated protective effects including modulation of autophagic response. Our findings provide new evidence highlighting an important role of the autophagic response in the EET-mediated survival of cardiac cells.
Language
English
DOI
doi:10.7939/R3804XR97
Rights
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication
Cell death & disease 4: e885, 2013

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