In vitro uptake of glutamate in GLAST- and GLT-1-transfected mutant CHO-K1 cells is inhibited by the ethylmercury-containing preservative thimerosal

Lysette Mutkus, Judy L. Aschner, Tore Syversen, Gouri Shanker, Ursula Sonnewald, Michael Aschner

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Thimerosal, also known as thimersal, Merthrolate, or sodiumethyl- mercurithiosalicylate, is an organic mercurial compound that is used in a variety of commercial as well as biomedical applications. As a preservative, it is used in a number of vaccines and pharmaceutical products. Its active ingredient is ethylmercury. Both inorganic and organic mercurials are known to interfere with glutamate homeostasis. Brain glutamate is removed mainly by astrocytes from the extracellular fluid via high-affinity astroglial Na +-dependent excitatory amino acid transporters, glutamate/ aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1). The effects of thimerosal on glutamate homeostasis have yet to be determined. As a first step in this process, we examined the effects of thimerosal on the transport of [3H]-D-aspartate, a nonmetabolizable glutamate analog, in Chinese hamster ovary (CHO) cells transfected with two glutamate transporter subtypes, GLAST (EAAT1) and GLT-1 (EAAT2). Additionally, studies were undertaken to determine the effects of thimerosal on mRNA and protein levels of these transporters. The results indicate that thimerosal treatment caused significant but selective changes in both glutamate transporter mRNA and protein expression in CHO cells. Thimerosal-mediated inhibition of glutamate transport in the CHO-K1 cell line DdB7 was more pronounced in the GLT-1-transfected cells compared with the GLAST-transfected cells. These studies suggest that thimerosal accumulation in the central nervous system might contribute to dysregulation of glutamate homeostasis.

Original languageEnglish (US)
Pages (from-to)71-86
Number of pages16
JournalBiological Trace Element Research
Volume105
Issue number1-3
StatePublished - Jun 2005
Externally publishedYes

Fingerprint

Thimerosal
Amino Acid Transport System X-AG
Cricetulus
Glutamic Acid
Ovary
Homeostasis
Cells
Amino Acid Transport Systems
D-Aspartic Acid
Messenger RNA
Excitatory Amino Acids
In Vitro Techniques
Extracellular Fluid
Neurology
Organic compounds
Astrocytes
Brain
Proteins
Vaccines
Central Nervous System

Keywords

  • Chinese hamster ovary (CHO) cells
  • Ethylmercury
  • Glutamate transport
  • Thimerosal

ASJC Scopus subject areas

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

Cite this

In vitro uptake of glutamate in GLAST- and GLT-1-transfected mutant CHO-K1 cells is inhibited by the ethylmercury-containing preservative thimerosal. / Mutkus, Lysette; Aschner, Judy L.; Syversen, Tore; Shanker, Gouri; Sonnewald, Ursula; Aschner, Michael.

In: Biological Trace Element Research, Vol. 105, No. 1-3, 06.2005, p. 71-86.

Research output: Contribution to journalArticle

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