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Permanent link (DOI): https://doi.org/10.7939/R3P55DP8G

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The Effect of Naphthoquinones on Gap Junctional Intercellular Communication Open Access

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Other title
Subject/Keyword
Intercellular Communication
Gap Junction
Naphthoquinones
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
AL Omair, Omar Abdulrahman
Supervisor and department
Klotz, Lars-Oliver (Faculty of Pharmacy & Pharmaceutical Sciences)
Examining committee member and department
Siraki, Arno (Pharmacy and Pharmaceutical Sciences)
Persad, Sujata (Department of Pediatrics)
Marsh, Sharon (Pharmacy and Pharmaceutical Sciences)
Department
Faculty of Pharmacy and Pharmaceutical Sciences
Specialization
Pharmaceutical Sciences
Date accepted
2014-09-24T15:50:43Z
Graduation date
2014-11
Degree
Master of Science
Degree level
Master's
Abstract
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.
Language
English
DOI
doi:10.7939/R3P55DP8G
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.
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