Next Article in Journal
Circulating Tumor Cells (CTC) and Cell-Free DNA (cfDNA) Workshop 2016: Scientific Opportunities and Logistics for Cancer Clinical Trial Incorporation
Next Article in Special Issue
MMP-3 Deficiency Alleviates Endotoxin-Induced Acute Inflammation in the Posterior Eye Segment
Previous Article in Journal
Pharmacogenomics in Pediatric Oncology: Review of Gene—Drug Associations for Clinical Use
Previous Article in Special Issue
Multifaceted Roles of ALG-2 in Ca2+-Regulated Membrane Trafficking
Article Menu
Issue 9 (September) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2016, 17(9), 1503; doi:10.3390/ijms17091503

Experimental Dissection of Metalloproteinase Inhibition-Mediated and Toxic Effects of Phenanthroline on Zebrafish Development

Department of Biology, University of New Brunswick, Fredericton, NB E3B 5A3, Canada
*
Author to whom correspondence should be addressed.
Academic Editor: Masatoshi Maki
Received: 28 July 2016 / Revised: 25 August 2016 / Accepted: 2 September 2016 / Published: 8 September 2016
(This article belongs to the Special Issue Metalloproteins 2017)
View Full-Text   |   Download PDF [12369 KB, uploaded 8 September 2016]   |  

Abstract

Metalloproteinases are zinc-dependent endopeptidases that function as primary effectors of tissue remodeling, cell-signaling, and many other roles. Their regulation is ferociously complex, and is exquisitely sensitive to their molecular milieu, making in vivo studies challenging. Phenanthroline (PhN) is an inexpensive, broad-spectrum inhibitor of metalloproteinases that functions by chelating the catalytic zinc ion, however its use in vivo has been limited due to suspected off-target effects. PhN is very similar in structure to phenanthrene (PhE), a well-studied poly aromatic hydrocarbon (PAH) known to cause toxicity in aquatic animals by activating the aryl hydrocarbon receptor (AhR). We show that zebrafish are more sensitive to PhN than PhE, and that PhN causes a superset of the effects caused by PhE. Morpholino knock-down of the AhR rescues the effects of PhN that are shared with PhE, suggesting these are due to PAH toxicity. The effects of PhN that are not shared with PhE (specifically disruption of neural crest development and angiogenesis) involve processes known to depend on metalloproteinase activity. Furthermore these PhN-specific effects are not rescued by AhR knock-down, suggesting that these are bona fide effects of metalloproteinase inhibition, and that PhN can be used as a broad spectrum metalloproteinase inhibitor for studies with zebrafish in vivo. View Full-Text
Keywords: metalloproteinase; phenanthroline; metalloproteinase inhibitor; zebrafish; aryl hydrocarbon receptor; poly aromatic hydrocarbon toxicity; angiogenesis; neural crest; in vivo study metalloproteinase; phenanthroline; metalloproteinase inhibitor; zebrafish; aryl hydrocarbon receptor; poly aromatic hydrocarbon toxicity; angiogenesis; neural crest; in vivo study
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Ellis, T.R.; Crawford, B.D. Experimental Dissection of Metalloproteinase Inhibition-Mediated and Toxic Effects of Phenanthroline on Zebrafish Development. Int. J. Mol. Sci. 2016, 17, 1503.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top