Copper related toxic effects on cellular protein metabolism in human astrocytes

Issue title: HNE and Further Lipid Peroxidation Products

Article type: Research Article

Authors: Merker, Katrin^; | Hapke, Doreen | Reckzeh, Kristian | Schmidt, Hartmut | Lochs, Herbert | Grune, Tilman^;

Affiliations: Neuroscience Research Center, Hepatology & Endocrinology Medical Faculty (Charité), Humboldt-University Berlin, Germany | Department of Gastroenterology, Hepatology & Endocrinology Medical Faculty (Charité), Humboldt-University Berlin, Germany | Research Institute of Environmental Medicine, Heinrich Heine University Duesseldorf, Germany

Note: [] Address for correspondence: Katrin Merker, Department of Gastroenterology, Hepatology & Endocrinology, Medical Faculty (Charité), Humboldt-University Berlin, Schumanstrasse 20-21, 10117 Berlin, Germany. Fax: +49 30 450 51 49 60; E-mail: [email protected]

Abstract: Introduction: Copper overload due to a defect in the ATPase 7B mediated copper excretion within hepatocytes produces the phenotype of Wilson disease. The overload of hepatocytes with copper results in necrotic liver cells and is accompanied by a high concentration of blood copper levels. That occurs to be the reason for increasing neurological copper concentration. Although copper is linked to oxidation, there are no data on the direct copper related effects in human brain cells. Aim: To test the copper induced changes in protein oxidation in human astrocyte like cells. Methods: We used U87 cells as model for human astrocytes. Cells were treated with increasing concentrations of copper(II)-chloride in Dulbeccos minimal essential medium. Subsequently, at different time points we investigated: cellular growth, cellular survival under copper treatment, the concentration of oxidized tryptophane in GADPH in vitro as well as the carbonyl concentration and the concentration of oxidized proteins in vivo in U87 glial cells. Results: The viability of cells decreased with both increasing copper concentration and duration of treatment. The concentration of oxidized proteins was directly correlated to the increase of copper concentration and duration of exposure. Conclusion: These observations demonstrate the similarities between copper treatment and treatment with other commonly used oxidants, including hydrogen peroxide. Furthermore, the vulnerability of astrocytes towards copper exposure could be demonstrated. Therefore, these data give further insights into understanding of copper metabolism, which in turn is important to reveal the exact pathological mechanism in copper related diseases such as Wilson disease.

Keywords: Oxidative stress, Wilson disease, astrocytes, copper induced oxidation

Journal: BioFactors, vol. 24, no. 1-4, pp. 255-261, 2005