METAL-INDUCED PROTEIN DENATURATION: REGULARITIES, PATHOLOGICAL MANIFESTATIONS, AND IN VITRO MODELING

Tetiana Popovych,Natalia Obernikhina,Natalia Voroshylova,Yaroslav Kizim

doi:10.32345/usmyj.4(127).2021.48-54

Abstract

the ability of various metal ions to form complexes with proteins leads to the denaturation of the latter and the development of immune response. Such hapten effects cause the well-known phenomenon of nickel-allergic contact dermatitis. No less typical are side effects of gadolinium compounds, that are used as contrasts for magnetic resonance imaging, but cause the development of fibrosis. In both cases an important role belongs to the interaction of metal ions with collagen structures. The aim of our study was to compare in vitro effects of copper and nickel ions on destabilized products of collagen cleavage. Significant difference between these metals in their ability to induce aggregation at close to physiological pH values was shown. The influence on the aggregative process of the acidification of the medium was revealed. It was shown that destabilization of protein structure leads to the formation of highly stabilized β-stacked protein aggregates. Comparison of the obtained experimental data with the literature ones makes it possible to approach the understanding of individual mechanisms of toxic effects of metal ions on the human body.

Highlights

Permanent rise of industrial burden on the environment causes the increase of the contact of living organisms with various toxic compounds
In recent years more and more attention is paid to the hapten properties of gadolinium ions Gd3+, which due to f-level of its electron shell and the ability to accumulate in diseased organs acquire the properties of magnetic resonance imaging (Todd & Kay, 2016)
It is shown that destabilized proteins tend to form stable β-structured aggregates, which are effectively detected by the specific dye Congo Red

Summary

Introduction

Permanent rise of industrial burden on the environment causes the increase of the contact of living organisms with various toxic compounds. The classic example of such kind of hapten effect is nickel-allergic contact dermatitis (Ni-ACD) It is detected by the contact of nickel-containing objects with human skin.The interaction of metals with biological fluids of the body (sweat, saliva, etc.) results in formatiom of free Ni2+ions, that denature the body’s proteins and cause a reaction of the immune system (Naumova, 2019; Morgan, 1989). In recent years more and more attention is paid to the hapten properties of gadolinium ions Gd3+, which due to f-level of its electron shell and the ability to accumulate in diseased organs acquire the properties of magnetic resonance imaging (Todd & Kay, 2016) This dramatically increases the informativeness of MRI diagnosis, but a side effect of the use of Gd3+ compounds is the development of fibrosis the growth of specific tissue, which differs significantly from normal ones (Wagner et al, 2016).

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