TY  - JOUR
A1  - Witt, Barbara
A1  - Stiboller, Michael
A1  - Raschke, Stefanie
A1  - Friese, Sharleen
A1  - Ebert, Franziska
A1  - Schwerdtle, Tanja
T1  - Characterizing effects of excess copper levels in a human astrocytic cell line with focus on oxidative stress markers
T2  - Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements, GMS
N2  - Background: Being an essential trace element, copper is involved in diverse physiological processes. However, excess levels might lead to adverse effects. Disrupted copper homeostasis, particularly in the brain, has been associated with human diseases including the neurodegenerative disorders Wilson and Alzheimer?s disease. In this context, astrocytes play an important role in the regulation of the copper homeostasis in the brain and likely in the prevention against neuronal toxicity, consequently pointing them out as a potential target for the neurotoxicity of copper. Major toxic mechanisms are discussed to be directed against mitochondria probably via oxidative stress. However, the toxic potential and mode of action of copper in astrocytes is poorly understood, so far. Methods: In this study, excess copper levels affecting human astrocytic cell model and their involvement in the neurotoxic mode of action of copper, as well as, effects on the homeostasis of other trace elements (Mn, Fe, Ca and Mg) were investigated. Results: Copper induced substantial cytotoxic effects in the human astrocytic cell line following 48 h incubation (EC30: 250 ?M) and affected mitochondrial function, as observed via reduction of mitochondrial membrane potential and increased ROS production, likely originating from mitochondria. Moreover, cellular GSH metabolism was altered as well. Interestingly, not only cellular copper levels were affected, but also the homeostasis of other elements (Ca, Fe and Mn) were disrupted. Conclusion: One potential toxic mode of action of copper seems to be effects on the mitochondria along with induction of oxidative stress in the human astrocytic cell model. Moreover, excess copper levels seem to interact with the homeostasis of other essential elements such as Ca, Fe and Mn. Disrupted element homeostasis might also contribute to the induction of oxidative stress, likely involved in the onset and progression of neurodegenerative disorders. These insights in the toxic mechanisms will help to develop ideas and approaches for therapeutic strategies against copper-mediated diseases.
KW  - Copper
KW  - Astrocytes
KW  - Toxicity
KW  - Mitochondria
KW  - ROS
KW  - Trace elements
Y1  - 2021
UR  - https://publishup.uni-potsdam.de/frontdoor/index/index/docId/61657
SN  - 1878-3252
VL  - 65
PB  - Elsevier
CY  - München
ER  -