The role of cytochrome P450 and the protective effect of EETs against isoproterenol-induced cellular hypertrophy in rat H9c2 cell line

  • Author / Creator
    Tse, Mandy M.Y.
  • Cytochrome P450 (CYP) enzymes have been identified in the heart and their levels have been reported to be altered during cardiac hypertrophy and heart failure. Furthermore, CYP enzymes have been shown to metabolize arachidonic acid to cardioprotective epoxyeicosatrienoic acids (EETs) and cardiotoxic 20-hydroxyeicosatetraenoic acid (20-HETE). Therefore, the objective of this study was to investigate the protective effect of EETs and the role of CYPs and soluble epoxide hydrolase (sEH) in the development of cardiac hypertrophy. Our results showed that isoproterenol-induced cellular hypertrophy caused a significant induction in the mRNA expression of CYP1A1, CYP1B1, CYP2J3, CYP4F4, CYP4F5 and EPHX2 in H9c2 cells. Also, we demonstrated that 11,12- and 14,15-EETs significantly attenuated the isoproterenol-mediated induction of hypertrophic markers, ANP and BNP, as well as CYP1A1, CYP2J3, CYP4F4, CYP4F5 and EPHX2. Furthermore, we showed that the inhibition of sEH by TUPS significantly decreased the isoproterenol-mediated induction of ANP, BNP, CYP1A1, CYP2J3, CYP4F4, CYP4F5 and EPHX2.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • 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.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Faculty of Pharmacy and Pharmaceutical Sciences
  • Specialization
    • Pharmaceutical Sciences
  • Supervisor / co-supervisor and their department(s)
    • Ayman, El-Kadi (Pharmacy and Pharmaceutical Sciences)
  • Examining committee members and their departments
    • Lars-Oliver, Klotz (Pharmacy and Pharmaceutical Sciences)
    • Glen, Baker (Psychiatry)
    • Paul, Jurasz (Pharmacy and Pharmaceutical Sciences)