title: Modulation of copper accumulation and copper-induced toxicity by antioxidants and copper chelators in cultured primary brain astrocytes.
abstract: Copper is essential for several important cellular processes, but an excess of copper can also lead to oxidative damage. In brain, astrocytes are considered to play a pivotal role in the copper homeostasis and antioxidative defence. To investigate whether antioxidants and copper chelators can modulate the uptake and the toxicity of copper ions in brain astrocytes, we used primary astrocytes as cell culture model. These cells accumulated substantial amounts of copper during exposure to copper chloride. Copper accumulation was accompanied by a time- and concentration-dependent loss in cell viability, as demonstrated by a lowering in cellular MTT reduction capacity and by an increase in membrane permeability for propidium iodide. During incubations in the presence of the antioxidants ascorbate, trolox or ebselen, the specific cellular copper content and the toxicity in copper chloride-treated astrocyte cultures were strongly increased. In contrast, the presence of the copper chelators bathocuproine disulfonate or tetrathiomolybdate lowered the cellular copper accumulation and the copper-induced as well as the ascorbate-accelerated copper toxicity was fully prevented. These data suggest that predominantly the cellular content of copper determines copper-induced toxicity in brain astrocytes.
authors: Center for Biomolecular Interactions Bremen, Faculty 2 (Biology/Chemistry), University of Bremen, PO Box 330440, D-28334 Bremen, Germany; Center for Environmental Research and Sustainable Technology, Leobener Strasse, D-28359 Bremen, Germany.
authors: Felix
authors: F
authors: Bulcke
authors: Department of Physiology (Cell Physiology Research Group), University of Extremadura, E-10003 Caceres, Spain.
authors: Patricia
authors: P
authors: Santofimia-Castaño
authors: Department of Physiology (Cell Physiology Research Group), University of Extremadura, E-10003 Caceres, Spain.
authors: Antonio
authors: A
authors: Gonzalez-Mateos
authors: Center for Biomolecular Interactions Bremen, Faculty 2 (Biology/Chemistry), University of Bremen, PO Box 330440, D-28334 Bremen, Germany; Center for Environmental Research and Sustainable Technology, Leobener Strasse, D-28359 Bremen, Germany. Electronic address: ralf.dringen@uni-bremen.de.
authors: Ralf
authors: R
authors: Dringen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000166:cytology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology*; D003300:Copper / Q000633:toxicity*; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013194:Staining and Labeling
chemical_list: D000975:Antioxidants; D002614:Chelating Agents; D017382:Reactive Oxygen Species; D003300:Copper
keywords: Antioxidants; Astrocytes; Chelators; Copper; ROS; Toxicity