Selenium homeostasis in human brain cells: Effects of copper (II) and Se species |
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| Affiliation: | 1. Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, Nuthetal 14558, Germany;2. Department of Molecular Nutritional Physiology, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Dornburger Str. 24, Jena 07743, Germany;3. TraceAge, DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly (FOR 2558), Potsdam, Jena, Berlin, Germany;4. German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Strasse 8-10, Berlin 10589, Germany;1. Department of Neurosurgery, 5th Military Clinical Hospital with the SP ZOZ Polyclinic in Krakow, 30-901 Krakow, Poland;2. Department of Histology, Cytophysiology and Embryology, Faculty of Medicine in Zabrze, Academy of Silesia in Katowice, 41-800 Zabrze, Poland;3. Department of Neurosurgery, St. Raphael Hospital, 30-693 Krakow, Poland;4. Department of Neurosurgery, Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski University, 30-705 Kraków, Poland;5. Department of Agricultural and Environmental Chemistry, University of Agriculture in Krakow, 31-120 Krakow, Poland;6. Department of Trauma and Orthopedic Surgery, 5th Military Clinical Hospital, Kraków, Poland;7. Department of Rehabilitation in Orthopedics, Faculty of Motor Rehabilitation Bronisław Czech University of Physical Education in Kraków, Poland;8. Department of Physiology, School of Medicine in Katowice, Medical University of Silesia, 40-752 Katowice, Poland;9. Department of Neurosurgery, Provincial Specialist Hospital No. 2 in Jastrzębie-Zdrój, 44-300 Jastrzębie-Zdrój, Poland;1. Poursina Hakim Digestive Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran;2. Immunology Department, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran;3. University of Debrecen, Medical School Hungary, Egyetem tér 1, Debrecen;4. Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;5. Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran;6. Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India;7. Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Science, Chennai 602105, India;8. University Institute of Pharma Sciences, Chandigarh University, Mohali, Punjab, India;9. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran;10. Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;11. School of Medicine, The University of Western Australia, Perth, Australia;12. Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran;1. Environmental Health Sciences Division, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA;2. Saba University School of Medicine, Caribbean, the Netherlands;3. Center for Environmental Occupational Risk Analysis and Management College of Public Health, University of South Florida, Tampa, FL, USA;4. Stantec (Cardno ChemRisk), Boston, MA, USA;5. Saint Francis Hospital and Medical Center; Hartford, CT, USA;6. School of Applied Meteorology, Nanjing University of Information Science & Technology, Nanjing 210044, China;7. Department of Biomedical and Biotechnological Sciences; School of Medicine University of Catania, Via Santa Sofia 97, Catania 95123, Italy;1. Graduate Group of Nutritional Biology, Department of Nutrition, University of California at Davis, One Shields Ave., Davis, CA 95616, USA;2. USDA/ARS/Western Human Nutrition Research Center, 430 West Health Sciences Drive, Davis, CA 95616, USA;3. Department of Pathology and Laboratory Medicine, University of California at Davis, 2805 50th Street, Sacramento, CA 95817, USA;1. Nuclear Energy Center for Agriculture, University of São Paulo, Avenida Centenário 303, 13416-000 Piracicaba, SP, Brazil;2. College of Agriculture Luiz de Queiroz, University of São Paulo, Avenida Pádua Dias 11, 13418-900 Piracicaba, SP, Brazil |
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| Abstract: | BackgroundBoth 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.MethodsFirstly, 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 (CuSO4) 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.ResultsModulation 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.ConclusionCu 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. |
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| Keywords: | Selenium Copper Interaction Brain Glutathione peroxidase Selenoprotein P |
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