Copper related toxic effects on cellular protein metabolism in human astrocytes.
BACKGROUND
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.


OBJECTIVE
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.


CONCLUSIONS
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.
Merker
Katrin
K
Neuroscience Research Center, Hepatology & Endocrinology Medical Faculty (Charité), Humboldt-University Berlin, Germany. katrin.merker@charite.de
Hapke
Doreen
D
Reckzeh
Kristian
K
Schmidt
Hartmut
H
Lochs
Herbert
H
Grune
Tilman
T
D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D001254:Astrocytoma; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000008:administration & dosage / Q000633:toxicity*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D010084:Oxidation-Reduction; D050050:Protein Carbonylation; D011506:Proteins / Q000378:metabolism*
D011506:Proteins; D003300:Copper; D006861:Hydrogen Peroxide; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; C029892:cupric chloride