Abstract
This short review will summarize the current knowledge on the uptake, storage, and export of copper ions by astrocytes and will address the potential roles of astrocytes in copper homeostasis in the normal and diseased brain. Astrocytes in culture efficiently accumulate copper by processes that include both the copper transporter Ctr1 and Ctr1-independent mechanisms. Exposure of astrocytes to copper induces an increase in cellular glutathione (GSH) content as well as synthesis of metallothioneins, suggesting that excess of copper is stored as complex with GSH and in metallothioneins. Furthermore, exposure of astrocytes to copper accelerates the release of GSH and glycolytically generated lactate. Astrocytes are able to export copper and express the Menkes protein ATP7A. This protein undergoes reversible, copper-dependent trafficking between the trans-Golgi network and vesicular structures. The ability of astrocytes to efficiently take up, store and export copper suggests that astrocytes play a key role in the supply of neurons with copper and that astrocytes should be considered as target for therapeutic interventions that aim to correct disturbances in brain copper homeostasis.
Highlights
Copper metabolism of astrocytesReviewed by: Alexej Verkhratsky, University of Manchester, UK Bogdan O
Astrocytes have many important functions in the brain, including the maintenance of extracellular ion homeostasis, the modulation of synaptic transmission and plasticity, the supply of metabolites, and the defense of the brain against oxidative stress and toxins (Parpura et al, 2012; Schmidt and Dringen, 2012)
Copper is essential for brain cells as a cofactor and structural component of various enzymes that are involved in important biochemical pathways such as the respiratory chain, the antioxidative defense and the iron metabolism (Scheiber and Dringen, 2013)
Summary
Reviewed by: Alexej Verkhratsky, University of Manchester, UK Bogdan O. This short review will summarize the current knowledge on the uptake, storage, and export of copper ions by astrocytes and will address the potential roles of astrocytes in copper homeostasis in the normal and diseased brain. Astrocytes are able to export copper and express the Menkes protein ATP7A. This protein undergoes reversible, copper-dependent trafficking between the trans-Golgi network and vesicular structures. The ability of astrocytes to efficiently take up, store and export copper suggests that astrocytes play a key role in the supply of neurons with copper and that astrocytes should be considered as target for therapeutic interventions that aim to correct disturbances in brain copper homeostasis
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