Induction of the mitochondrial permeability transition in cultured astrocytes by glutamine

K. V. Rama Rao, A. R. Jayakumar, M. D. Norenberg

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

Ammonia is a toxin that has been strongly implicated in the pathogenesis of hepatic encephalopathy (HE), and astrocytes appear to be the principal target of ammonia toxicity. Glutamine, a byproduct of ammonia metabolism, has been implicated in some of the deleterious effects of ammonia on the CNS. We have recently shown that ammonia induces the mitochondrial permeability transition (MPT) in cultured astrocytes, but not in neurons. We therefore determined whether glutamine is also capable of inducing the MPT in cultured astrocytes. Astrocytes were treated with glutamine (4.5mM) for various time periods and the MPT was assessed by changes in 2-deoxyglucose (2-DG) mitochondrial permeability, calcein fluorescence assay, and by changes in cyclosporin A (CsA)-sensitive inner mitochondrial membrane potential (ΔΨm) using the potentiometric dye, JC-1. Astrocytes treated with glutamine significantly increased 2-DG permeability (120%, P<0.01), decreased mitochondrial calcein fluorescence, and concomitantly dissipated the ΔΨm. All of these effects were blocked by CsA. These data indicate that glutamine induces the MPT in cultured astrocytes. The induction of the MPT by glutamine in astrocytes, and the subsequent development of mitochondrial dysfunction, may partially explain the deleterious affects of glutamine on the CNS in the setting of hyperammonemia.

Original languageEnglish (US)
Pages (from-to)517-523
Number of pages7
JournalNeurochemistry International
Volume43
Issue number4-5
DOIs
StatePublished - Jan 1 2003

Keywords

  • Ammonia
  • Astrocytes
  • Glutamine
  • Hepatic encephalopathy
  • Mitochondrial permeability transition

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Cellular and Molecular Neuroscience

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