Copper transporters are responsible for copper isotopic fractionation in eukaryotic cells
| Autor: | Alexandre Soulard, Sylvain Pichat, Philippe Oger, Victor P. Bondanese, Jean-Loup Cadiou, Francis Albarède, Toshiyuki Fujii |
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| Přispěvatelé: | Laboratoire de Géologie de Lyon - Terre, Planètes, Environnement [Lyon] (LGL-TPE), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon), Génétique moléculaire des levures (YMG), Microbiologie, adaptation et pathogénie (MAP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Graduate School of Engineering, Osaka University, Graduate School of Engineering, Laboratoire de Géologie de Lyon - Terre, Planètes, Environnement (LGL-TPE), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut national des sciences de l'Univers (INSU - CNRS)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Carcinoma Hepatocellular Isotopes of copper [SDV]Life Sciences [q-bio] chemistry.chemical_element Cell Cycle Proteins Saccharomyces cerevisiae Fractionation Reductase Article 03 medical and health sciences Isotope fractionation Neoplasms Humans Cation Transport Proteins Copper Transporter 1 Oncogene Proteins chemistry.chemical_classification Multidisciplinary 030102 biochemistry & molecular biology Isotope Liver Neoplasms Membrane Transport Proteins Copper Amino acid Eukaryotic Cells 030104 developmental biology Copper Radioisotopes Biochemistry chemistry Dose Fractionation Radiation Oxidoreductases Sulfur Cysteine |
| Zdroj: | Scientific Reports Scientific Reports, Nature Publishing Group, 2017, 7, ⟨10.1038/srep44533⟩ Scientific Reports, 2017, 7, ⟨10.1038/srep44533⟩ |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep44533⟩ |
| Popis: | Copper isotopic composition is altered in cancerous compared to healthy tissues. However, the rationale for this difference is yet unknown. As a model of Cu isotopic fractionation, we monitored Cu uptake in Saccharomyces cerevisiae, whose Cu import is similar to human. Wild type cells are enriched in 63Cu relative to 65Cu. Likewise, 63Cu isotope enrichment in cells without high-affinity Cu transporters is of slightly lower magnitude. In cells with compromised Cu reductase activity, however, no isotope fractionation is observed and when Cu is provided solely in reduced form for this strain, copper is enriched in 63Cu like in the case of the wild type. Our results demonstrate that Cu isotope fractionation is generated by membrane importers and that its amplitude is modulated by Cu reduction. Based on ab initio calculations, we propose that the fractionation may be due to Cu binding with sulfur-rich amino acids: methionine and cysteine. In hepatocellular carcinoma (HCC), lower expression of the STEAP3 copper reductase and heavy Cu isotope enrichment have been reported for the tumor mass, relative to the surrounding tissue. Our study suggests that copper isotope fractionation observed in HCC could be due to lower reductase activity in the tumor. |
| Databáze: | OpenAIRE |
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