Selenium homeostasis in human brain cells: Effects of copper (II) and Se species.

Autor: Raschke S; Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, Nuthetal 14558, Germany., Ebert F; Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, Nuthetal 14558, Germany., Kipp AP; Department of Molecular Nutritional Physiology, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Dornburger Str. 24, Jena 07743, Germany; TraceAge, DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly (FOR 2558), Potsdam, Jena, Berlin, Germany., Kopp JF; Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, Nuthetal 14558, Germany; TraceAge, DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly (FOR 2558), Potsdam, Jena, Berlin, Germany., Schwerdtle T; Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, Nuthetal 14558, Germany; TraceAge, DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly (FOR 2558), Potsdam, Jena, Berlin, Germany; German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Strasse 8-10, Berlin 10589, Germany. Electronic address: tanja.schwerdtle@uni-potsdam.de.
Jazyk: angličtina
Zdroj: Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) [J Trace Elem Med Biol] 2023 Jul; Vol. 78, pp. 127149. Date of Electronic Publication: 2023 Mar 12.
DOI: 10.1016/j.jtemb.2023.127149
Abstrakt: Background: Both essential trace elements selenium (Se) and copper (Cu) play an important role in maintaining brain function. Homeostasis of Cu, which is tightly regulated under physiological conditions, seems to be disturbed in Alzheimer´s (AD) and Parkinson´s disease (PD) patients. Excess Cu promotes the formation of oxidative stress, which is thought to be a major cause for development and progression of neurological diseases (NDs). Most selenoproteins exhibit antioxidative properties and may counteract oxidative stress. However, expression of selenoproteins is altered under conditions of Se deficiency. Serum Se levels are decreased in AD and PD patients suggesting Se as an important factor in the development and progression of NDs. The aim of this study was to elucidate the interactions between Cu and Se in human brain cells particularly with respect to Se homeostasis.
Methods: Firstly, modulation of Se status by selenite or SeMet were assessed in human astrocytes and human differentiated neurons. Therefore, cellular total Se content, intra- and extracellular selenoprotein P (SELENOP) content, and glutathione peroxidase (GPX) activity were quantified. Secondly, to investigate the impact of Cu on these markers, cells were exposed to copper(II)sulphate (CuSO 4 ) for 48 h. In addition, putative protective effects of Se on Cu-induced toxicity, as measured by cell viability, DNA damage, and neurodegeneration were investigated.
Results: Modulation of cellular Se status was strongly dependent on Se species. In detail, SeMet increased total cellular Se and SELENOP content, whereas selenite led to increased GPX activity and SELENOP excretion. Cu treatment resulted in 133-fold higher cellular Cu concentration with a concomitant decrease in Se content. Additionally, SELENOP excretion was suppressed in both cell lines, while GPX activity was diminished only in astrocytes. These effects of Cu could be partially prevented by the addition of Se depending on the cell line and Se species used. While Cu-induced oxidative DNA damage could not be prevented by addition of Se regardless of chemical species, SeMet protected against neurite network degeneration triggered by Cu.
Conclusion: Cu appears to negatively affect Se status in astrocytes and neurons. Especially with regard to an altered homeostasis of those trace elements during aging, this interaction is of high physiological relevance. Increasing Cu concentrations associated with decreased selenoprotein expression or functionality might be a promoting factor for the development of NDs.
Competing Interests: Declaration of interest The authors declare no conflicts of interest.
(Copyright © 2023. Published by Elsevier GmbH.)
Databáze: MEDLINE
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