Different preferences in the utilization of amino acids for glutathione synthesis in cultured neurons and astroglial cells derived from rat brain

Kranich, Oliver; Hamprecht, Bernd; Dringen, Ralf

doi:10.1016/s0304-3940(96)13217-1

Cited by 94 publications

(81 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alternatively, the efflux have different cellular origin. Glutathione is present in both neurons and glia (29,30,(82)(83)(84)(85)(86), but as no functional NMDA receptors appear to be located on hippocampal glia cells (87), the most straightforward explanation for the increase in glutathione efflux is neuronal release. However, it cannot be excluded that NMDA-receptor stimulation induces a release of a substance from neurons that evokes glutathione release from the glial cells.…”

Section: Discussionmentioning

confidence: 99%

“…Glutathione may also increase NMDA receptor responses by interacting with its redox sites (26)(27)(28). Furthermore, because the breakdown products of glutathione include cysteine, glycine, and cysteineglycine, extracellular breakdown may supply surrounding cells with these glutathione precursors (29)(30)(31). Despite the key function of glutathione in intracellular redox regulation and the putative extracellular effects in brain, the mechanisms and factors determining the efflux remain unknown.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Searching for Mechanisms of N-Methyl-d-Aspartate-Induced Glutathione Efflux in Organotypic Hippocampal Cultures

et al. 2003

View full text Add to dashboard Cite

N-Methyl-D-aspartate (NMDA)-receptor stimulation evoked a selective and partly delayed elevated efflux of glutathione, phosphoethanolamine, and taurine from organotypic rat hippocampus slice cultures. The protein kinase inhibitors H9 and staurosporine had no effect on the efflux. The phospholipase A 2 inhibitors quinacrine and 4-bromophenacyl bromide, as well as arachidonic acid, a product of phospholipase A 2 activity, did not affect the stimulated efflux. Polymyxin B, an antimicrobal agent that inhibits protein kinase C, and quinacrine in high concentration (500 μM), blocked efflux completely. The stimulated efflux after but not during NMDA incubation was attenuated by a calmodulin antagonist (W7) and an anion transport inhibitor (DNDS). Omission of calcium increased the spontaneous efflux with no or small additional effects by NMDA. In conclusion, NMDA receptor stimulation cause an increased selective efflux of glutathione, phosphoethanolamine and taurine in organotypic cultures of rat hippocampus. The efflux may partly be regulated by calmodulin and DNDS sensitive channels.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Searching for Mechanisms of N-Methyl-d-Aspartate-Induced Glutathione Efflux in Organotypic Hippocampal Cultures

et al. 2003

View full text Add to dashboard Cite

show abstract

“…Extracellular supplies of the other two precursors, glutamate and glycine, do not increase GSH synthesis (3,42) because of their higher intracellular concentrations. Another precursor for the glutamate moiety of GSH is glutamine (43). The activity of glutaminase, which generates glutamate from glutamine, is reportedly higher in neurons than in astrocytes (44).…”

Section: Gsh Synthesismentioning

confidence: 99%

“…The dipeptide CysGly is hydrolyzed by neuronal dipeptidase into cysteine and glycine (42,60). Neurons utilize cysteine but not cystine for GSH synthesis, whereas glial cells utilize both (43,54). The CSF cysteine concentration was much higher than that of cystine (56).…”

Section: Cysteine Uptakementioning

confidence: 99%

Regulation of Neuronal Glutathione Synthesis

2008

View full text Add to dashboard Cite

Abstract. The brain is among the major organs generating large amounts of reactive oxygen species and is especially susceptible to oxidative stress. Glutathione (GSH) plays critical roles as an antioxidant, enzyme cofactor, cysteine storage form, the major redox buffer, and a neuromodulator in the central nervous system. GSH deficiency has been implicated in neurodegenerative diseases. GSH is a tripeptide comprised of glutamate, cysteine, and glycine. Cysteine is the rate-limiting substrate for GSH synthesis within neurons. Most neuronal cysteine uptake is mediated by sodium-dependent excitatory amino acid transporter (EAAT) systems, known as excitatory amino acid carrier 1 (EAAC1). Previous studies demonstrated EAAT is vulnerable to oxidative stress, leading to impaired function. A recent study found EAAC1-deficient mice to have decreased brain GSH levels and increased susceptibility to oxidative stress. The function of EAAC1 is also regulated by glutamate transporter associated protein 3-18. This review focuses on the mechanisms underlying GSH synthesis, especially those related to neuronal cysteine transport via EAAC1, as well as on the importance of GSH functions against oxidative stress.

show abstract

“…A second unusual aspect of glutathione synthesis in the brain is the unique metabolic interaction between astrocytes and neurons regarding uptake of cysteine, the rate-limiting amino acid for glutathione synthesis (Dringen and Hirrlinger, 2003;Kranich et al, 1996). Astrocytes and neurons have different affinities for the uptake of oxidized and reduced forms of cysteine for glutathione synthesis (Dringen et al, 2000b).…”

Section: Introductionmentioning

confidence: 99%

Thimerosal Neurotoxicity is Associated with Glutathione Depletion: Protection with Glutathione Precursors

et al. 2005

View full text Add to dashboard Cite

Different preferences in the utilization of amino acids for glutathione synthesis in cultured neurons and astroglial cells derived from rat brain

Cited by 94 publications

References 15 publications

Searching for Mechanisms of N-Methyl-d-Aspartate-Induced Glutathione Efflux in Organotypic Hippocampal Cultures

Searching for Mechanisms of N-Methyl-d-Aspartate-Induced Glutathione Efflux in Organotypic Hippocampal Cultures

Regulation of Neuronal Glutathione Synthesis

Thimerosal Neurotoxicity is Associated with Glutathione Depletion: Protection with Glutathione Precursors

Contact Info

Product

Resources

About