Abstract
Various pathological processes in humans are associated with biogenic iron accumulation and the mineralization of iron oxide nanoparticles, especially magnetite. Ferritin has been proposed as a precursor to pathological magnetite mineralization. This study quantifies spectroscopically the release of ferrous ions from native ferritin and magnetoferritin as a model system for pathological ferritin in the presence of potent natural reducing agents (vitamins C and B2) over time. Ferrous cations are required for the transformation of ferrihydrite (physiological) into a magnetite (pathological) mineral core and are considered toxic at elevated levels. The study shows a significant difference in the reduction and iron release from native ferritin compared to magnetoferritin for both vitamins. The amount of reduced iron formed from a magnetoferritin mineral core is two to five times higher than from native ferritin. Surprisingly, increasing the concentration of the reducing agent affects only iron release from native ferritin. Magnetoferritin cores with different loading factors seem to be insensitive to different concentrations of vitamins. An alternative hypothesis of human tissue magnetite mineralization and the process of iron-induced pathology is proposed. The results could contribute to evidence of the molecular mechanisms of various iron-related pathologies, including neurodegeneration.
Highlights
Iron played a role in the origin of life on Earth [1] and, except for Lactobacillus and certain strains of Bacillus [2], it is an essential element for living organisms [3]
To find a possible transformation mechanism, this study focused on vitamin C and vitamin B2, which are biologically essential molecules capable of reducing ferritin’s mineral core; they are present in relatively high concentrations in cells [33,34]
Nanoparticles possess an electrical bilayer that is dependent on their concentration, and the pH and ionic strength of the surrounding medium; the of ferritin particles is greater than native apoferritin biomacromolecules (10–12 nm)
Summary
Iron played a role in the origin of life on Earth [1] and, except for Lactobacillus and certain strains of Bacillus [2], it is an essential element for living organisms [3]. It is involved in many fundamental metabolic processes such as photosynthesis, respiration, DNA synthesis, cell proliferation, and differentiation. It is generally accepted that the toxicity of iron results from the ability of ferrous ions to produce hydroxyl radicals through the Fenton and Haber–Weis reactions [9]. It is widely accepted that disrupted iron homeostasis results in iron accumulation [6,15] and the mineralization of nanosized iron oxide particles, in particular as magnetite [16]
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