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

Lysette Mutkus, Judy L. Aschner, Vanessa Fitsanakis, Michael Aschner

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)221-230
Number of pages10
JournalBiological Trace Element Research
Volume107
Issue number3
DOIs
StatePublished - Dec 2005
Externally publishedYes

Fingerprint

Amino Acid Transport System X-AG
Manganese
Cricetulus
Glutamic Acid
Ovary
Brain
Neurology
Aspartic Acid
Astrocytes
Excitatory Amino Acid Transporter 1
Homeostasis
Central Nervous System
Cells
Amino Acid Transport Systems
D-Aspartic Acid
Excitatory Amino Acids
Essential Amino Acids
In Vitro Techniques
Extracellular Fluid
Metabolism

Keywords

  • Chinese hamster ovary cells
  • Glutamate transporters
  • Manganese

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

The in vitro uptake of glutamate in GLAST and GLT-1 transfected mutant CHO-K1 cells is inhibited by manganese. / Mutkus, Lysette; Aschner, Judy L.; Fitsanakis, Vanessa; Aschner, Michael.

In: Biological Trace Element Research, Vol. 107, No. 3, 12.2005, p. 221-230.

Research output: Contribution to journalArticle

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