Copper related toxic effects on cellular protein metabolism in human astrocytes
Copper related toxic effects on cellular protein metabolism in human astrocytes
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DOI：
10.1002/biof.5520240130
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发表时间：
2005-01-01
期刊：
影响因子：
6
通讯作者：
Grune, T
中科院分区：
文献类型：
--
作者：
Merker, K;Hapke, D;Grune, T
导言：肝细胞内atp酶7B介导的铜排泄缺陷导致铜超载，产生Wilson病的表型。肝细胞的铜超载导致坏死的肝细胞，并伴有高浓度的血铜水平。这似乎是神经系统铜浓度增加的原因。虽然铜与氧化有关，但没有数据表明铜对人类脑细胞的直接影响。目的：探讨铜对星形胶质细胞样细胞蛋白氧化的影响。方法：以U87细胞为人星形胶质细胞模型。细胞在Dulbeccos最小必需培养基中用增加浓度的氯化铜（II）处理。随后，我们在不同的时间点研究了U87胶质细胞的细胞生长、铜处理下的细胞存活、体外GADPH中氧化色氨酸的浓度以及体内羰基浓度和氧化蛋白的浓度。结果：细胞活力随铜浓度的增加和处理时间的延长而降低。氧化蛋白的浓度与铜浓度的增加和暴露时间直接相关。结论：这些观察结果证明了铜处理与其他常用氧化剂（包括过氧化氢）处理之间的相似性。此外，星形胶质细胞对铜暴露的脆弱性可以被证明。因此，这些数据有助于进一步了解铜代谢，从而揭示铜相关疾病（如Wilson病）的确切病理机制。
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.