Elevation of glutathione levels by ammonium ions in primary cultures of rat astrocytes

Ch R.K. Murthy, Alex S. Bender, Roy S. Dombro, Ge Bai, Michael D. Norenberg

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

It is well established that ammonia is detoxified in the brain to form glutamine and that astrocytes play a major role in this process. The synthesis of glutamine requires glutamate and ATP. Since glutamate and ATP are also required for the synthesis of glutathione (GSH), we examined the effect of pathophysiological concentrations of ammonia on levels of GSH in primary cultures of astrocytes. GSH content in the medium increased in a dose- and time-dependent manner in the presence of ammonia. After an initial decrease, cellular GSH content increased in a similar manner. The levels of glutathione disulfide (GSSG) were also increased. A linear relationship was observed between ammonia concentration and the increase in GSH levels. An increase in the efflux of GSH from cells into medium was also observed under these conditions. Buthionine sulfoximine and acivicin, but not methionine sulfoximine, blocked the ammonia induced increase in GSH levels. No, or minor, changes in the activities of enzymes (γ-glutamyl transpeptidase, GSH reductase and GSH-peroxidase) that might influence GSH levels were identified and thus could not account for the ammonia induced increase in GSH levels in astrocytes. These findings indicate that pathophysiological concentrations of ammonium ions result in increased astroglial levels of GSH which may affect the metabolism and function of astrocytes.

Original languageEnglish (US)
Pages (from-to)255-268
Number of pages14
JournalNeurochemistry International
Volume37
Issue number2-3
DOIs
StatePublished - Aug 1 2000

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Keywords

  • Ammonia
  • Astrocytes
  • Free radicals
  • Glutathione
  • Hepatic encephalopathy

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Cellular and Molecular Neuroscience

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