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

• Author / Creator

  Alsaleh, Nasser B

• 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.

• Subjects / Keywords

  • Epoxyeicosatrienoic acids
  • Neonatal Cardiomyocytes
  • Autophagy
  • Starvation
  • HL-1 cells

• Graduation date

  Spring 2014

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3804XR97

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.