The Effect of Naphthoquinones on Gap Junctional Intercellular Communication

  • Author / Creator
    AL Omair, Omar Abdulrahman
  • Gap junctions are groups of channels that connect two neighboring cells, allowing for the passage of small molecules, such as nutrients and signalling factors, between cytosols. Gap junctional channels consist of building blocks called connexins. Cancer cells exhibit a low basal level of gap junctional intercellular communication (GJIC), and experimental animals that lack certain connexins were shown to develop cancer at faster rates than their healthy counterparts. Here, we investigate the effect of synthetic and natural naphthoquiones on connexin43 and on GJIC in order to identify potential modes of interference of quinoid compounds with cellular pathways that control GJIC. WB-F344 rat liver epithelial cells were exposed to synthetic and natural naphthoquinones. Phosphorylation of connexin-43, the epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinases (ERK-1, -2), were analysed by Western blotting. Naphthoquinone toxicity profiles were established using neutral red uptake for assessment of cell viability. Assessment of GJIC was performed by microinjection of a channel-permeant fluorescent dye, Lucifer yellow, into single cells and microscopic analysis of its spreading to cells adjacent to injected cells. Of the naphthoquinones tested, menadione (2-methyl-1,4-naphthoquinone, MQ), 2-methoxy-1,4-naphthoquinone (MNQ) and 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) caused a significant phosphorylation of connexin-43 at different concentrations. In line with this, GJIC was significantly downregulated after 20 min of exposure to MQ, MNQ or DMNQ. In conclusion, Redox-cycling naphthoquinones (with exclusive redox-cyclers, such as DMNQ, and alkylating/redox-cycling naphthoquinones, such as MQ and MNQ) stimulate connexin phosphorylation and a loss of GJIC.

  • 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)
    • Klotz, Lars-Oliver (Faculty of Pharmacy & Pharmaceutical Sciences)
  • Examining committee members and their departments
    • Persad, Sujata (Department of Pediatrics)
    • Siraki, Arno (Pharmacy and Pharmaceutical Sciences)
    • Marsh, Sharon (Pharmacy and Pharmaceutical Sciences)