Endothelial Antioxidant-1: a Key Mediator of Copper-dependent Wound Healing in vivo

For most of us, when we suffer a cut or a wound, the healing process occurs over a period of a few days and happens without us taking much notice. We recognize the different phases: first it swells up, then it scabs over, and eventually the tissue repairs itself to make it seem as though nothing really happened. However, this relatively straightforward process most of us witness on a daily basis is far from simple. It is the result of a series of complex biological processes carried out with a wide array of substances. Understanding this process and how each of the different substances involved interact with each other is a useful way to help promote more effective wound healing techniques. Copper (Cu) is a nutrient that is known to play a key role in wound healing, particularly because of its inclusion in the process known as angiogenesis. It stimulates cell proliferation and migration, and Cu chelation has been shown to inhibit tumor growth angiogenic responses, as well as to treat Wilson's disease. The role Cu plays in these processes is understood, but what is still not clear is the exact mechanism by which exogenous or endogenous Cu promotes wound angiogenesis and inflammation that is required for tissue repair. However, in excess, Cu can be toxic, so the body has a number of different ways of regulating Cu quantities to make sure it is not doing more harm than good.

This was the focus of the study performed by Das et al. from the University of Illinois at Chicago. The team looked at the role of Antioxidant-1 (Atox1) in wound healing using cutaneous wound healing model with Atox1−/− and EC-specific Atox1−/− mice as well as Atox1−/− mice treated with gene transfer of nuclear-target Atox1. Atox1 is known as a Cu chaperone because it helps transport it to where the body needs it. Part of this process involves delivering Cu to secretory Cu-dependent enzymes such as extracellular superoxide dismutase (ecSOD) or lysyl oxidase (LOX). As such, measuring LOX is one of the critical processes in this type of study, which was done using the Amplite Fluorimetric Lysyl Oxidase Assay Kit. By using a sensitive fluorescent assay activated by Amplite's LOX substrate, this kit limits the interference that can sometimes occur in biological samples, allowing for more reliable results.

This study concluded that Atox1 in fact senses Cu to accelerate wound healing by promoting ROS, inflammatory cell recruitment and cell proliferation. What this means is that enhancing the Cu-Atox1-mediated therapy may turn out to be a new and more effective way to promote skin healing that is dependent on angiogenesis and inflammation. This is something that stands to genuinely improve people's lives and was made possible by the instruments that allow researchers to so closely monitor the complex biological processes of the human body. By being able to closely measure LOX, this research team was able to see the true effects of Atox1, giving confidence in the therapy options that could be developed from this study.

References

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1. Das, Archita, et al. "Endothelial antioxidant-1: A key mediator of copper-dependent wound healing in vivo." Scientific reports 6 (2016): 33783.