Strbak Oliver, Balejcikova Lucia, Kmetova Martina, Gombos Jan, Trancikova Alzbeta, Pokusa Michal, Kopcansky Peter
Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4, 036 01 Martin, Slovakia.
Institute of Hydrology, Slovak Academy of Sciences, Dubravska cesta 9, 841 04 Bratislava, Slovakia.
Int J Mol Sci. 2020 Aug 31;21(17):6332. doi: 10.3390/ijms21176332.
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 B) 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.
人类的各种病理过程与生物源铁积累及氧化铁纳米颗粒(尤其是磁铁矿)的矿化有关。铁蛋白被认为是病理性磁铁矿矿化的前体。本研究通过光谱法定量分析了在强效天然还原剂(维生素C和B)存在下,随着时间推移,天然铁蛋白和磁铁蛋白作为病理性铁蛋白模型系统中二价铁离子的释放情况。二价阳离子是将水铁矿(生理性)转化为磁铁矿(病理性)矿核所必需的,且在高浓度时被认为具有毒性。研究表明,对于这两种维生素,天然铁蛋白与磁铁蛋白在还原和铁释放方面存在显著差异。由磁铁蛋白矿核形成的还原铁量比天然铁蛋白高出两到五倍。令人惊讶的是,增加还原剂浓度仅影响天然铁蛋白的铁释放。不同负载因子的磁铁蛋白核心似乎对不同浓度的维生素不敏感。本文提出了关于人体组织磁铁矿矿化及铁诱导病理过程的另一种假说。这些结果可能有助于为包括神经退行性变在内的各种铁相关病理的分子机制提供证据。