The trace element selenium (Se) was discovered by the Swedish scientist Jöns Jacob Berzelius in 1817. Its essentiality was discovered in 1957 by Schwarz and Foltz. In biological systems, Se exerts its essential role as the 21st amino acid, selenocysteine (Sec). Because Sec differs from cysteine (Cys) only by the replacement of sulphur for Se and because Cys incorporation presents a canonical translational insertion, the actual biological advantage of selenolate-based over thiolate-based catalysis has remained elusive. Anyhow, as part of the gluthadione peroxidase, selenium is known as an antioxidant that protects several cell types in mammals, fish, birds, nematodes and bacteria from oxidative breakdown.
While the essentiality of selenium for humans, many animals and some bacteria is well known since about 60 years, the research team around
Marcus Conrad (team leader at the Institute for Developmental Genetics, IDG at the Helmholtz Zentrum München) together with Carsten Berndt (Molekulare Neurologie - Universitätsklinikum Düsseldorf) and Gereon Poschmann (Molecular Proteomics Laboratory, Heinrich-Heine Universität) were able to show why.
In the framework of the DFG funded program „Dynamics of Thiol-based Redox Switches in Cellular Physiology“ the researchers are investigating the role of oxidoreductases for the development of neurons and especially the cell death induced by the presence of iron (ferroptose). In order to study the role of the enzyme glutathione peroxidase 4 (GPX4), one of the 25 selenoproteins in humans, the researchers developed a mouse model with modified GPX4.
Figure:
The GPX4-Cys variant is highly susceptible to hydroperoxide-induced inactivation - Hydroperoxide induces ferroptosis in Gpx4cys/cys cells - Selenium-containing GPX4 is necessary for full viability of mice
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They observed that animals with modified GPX4, having incorporated sulphur instead of selenium, were not living for more than 3 weeks. Searching for the reason of death, they found certain neuron types were missing, which were broken down during brain development induced by ferroptosis.
The original publication:
Irina Ingold, Carsten Berndt, Sabine Schmitt, Sebastian Doll, Gereon Poschmann, Katalin Buday, Antonella Roveri, Xiaoxiao Peng, Florencio Porto Freitas, Tobias Seibt, Lisa Mehr, Michaela Aichler, Axel Walch, Daniel Lamp, Martin Jastroch, Sayuri Miyamoto, Wolfgang Wurst, Fulvio Ursini, Elias S.J. Arnér, Noelia Fradejas-Villar, Ulrich Schweizer, Hans Zischka, José Pedro Friedmann Angeli, Marcus Conrad,
Selenium Utilization by GPX4 Is Required to Prevent Hydroperoxide-Induced Ferroptosis, Cell, 2018. doi: 10.1016/j.cell.2017.11.048
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Link database: Selenium and human health
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last time modified: September 22, 2024
