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National Institute of Environmental Health Sciences

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Publication Detail

Title: The in vitro uptake of glutamate in GLAST and GLT-1 transfected mutant CHO-K1 cells is inhibited by manganese.

Authors: Mutkus, Lysette; Aschner, Judy L; Fitsanakis, Vanessa; Aschner, Michael

Published In Biol Trace Elem Res, (2005 Dec)

Abstract: In the central nervous system (CNS), extracellular concentrations of amino acids (e.g., aspartate, glutamate) and divalent metals (e.g., zinc, copper, manganese) are primarily regulated by astrocytes. Adequate glutamate homeostasis and control over extracellular concentrations of these excitotoxic amino acids are essential for the normal functioning of the brain. Not only is glutamate of central importance for nitrogen metabolism but, along with aspartate, it is the primary mediator of excitatory pathways in the brain. Similarly, the maintenance of proper Mn levels is important for normal brain function. Brain glutamate is removed from the extracellular fluid mainly by astrocytes via high affinity astroglial Na+-dependent excitatory amino acid transporters, glutamate/aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1). The effects of Mn on specific glutamate transporters have yet to be determined. As a first step in this process, we examined the effects of Mn on the transport of [D-2, 3-3H]D-aspartate, a non-metabolizable glutamate analog, in Chinese hamster ovary cells (CHO) transfected with two glutamate transporter subtypes, GLAST (EAAT1) or GLT-1 (EAAT2). Mn-mediated inhibition of glutamate transport in the CHO-K1 cell line DdB7 was pronounced in both the GLT-1 and GLAST transfected cells. This resulted in a statistically significant inhibition (p<0.05) of glutamate uptake compared with transfected control in the absence of Mn treatment. These studies suggest that Mn accumulation in the CNS might contribute to dysregulation of glutamate homeostasis.

PubMed ID: 16286678 Exiting the NIEHS site

MeSH Terms: Amino Acids/metabolism; Animals; Astrocytes/metabolism; Brain/metabolism; CHO Cells; Cells, Cultured; Central Nervous System/metabolism; Chlorides/chemistry; Cricetinae; D-Aspartic Acid/chemistry; Excitatory Amino Acid Transporter 1/metabolism; Excitatory Amino Acid Transporter 2/metabolism; Glutamates/metabolism; Glutamic Acid/chemistry*; Glutamic Acid/metabolism; Glutamic Acid/pharmacokinetics*; In Vitro; Manganese Compounds/chemistry; Manganese/chemistry*; Manganese/metabolism; Mutation; Neurons/metabolism; Research Support, N.I.H., Extramural; Substantia Nigra/metabolism; Time Factors; Trace Elements; Transfection

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