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Brennan L, Alves PM, Hewage C, Malthouse JP,
McBean GJ.
Impact of the gliotoxin L-serine-O-sulphate on cellular metabolism
in cultured rat astrocytes.
Neurochem
Int. 2006 Jun;48(8):739-45. Epub 2006 Feb 2.
UCD School of Biomolecular and Biomedical Sciences, UCD Conway
Institute of Biomolecular and Biomedical Research, University College
Dublin, Belfield, Dublin 4, Ireland.
L-serine-O-sulphate is a member of a group of amino acids collectively
called gliotoxins and is a substrate for the high affinity
sodium-dependent glutamate transporters. Previous studies have shown
that it is toxic to primary cultures of astrocytes but the mode of
toxicity is unknown. The current study demonstrates that L-serine-O-sulphate,
at a sub-toxic concentration (400 microM), causes significant disruption
to glucose and alanine metabolism in cultures of rat cortical astrocytes.
More specifically, using (13)C NMR spectroscopy a significant reduction
in labelled end products from [1-(13)C]glucose and [3-(13)C]alanine was
found in the presence of L-serine-O-sulphate. Additionally, using
[2-(13)C]glycine a 27% reduction in de novo glutathione synthesis was
observed in the presence of the gliotoxin. Incubation of the cells with
L-serine-O-sulphate reduced the activity of alanine and aspartate
aminotransferase by 53% and 67%, respectively. Collectively these
results show that the gliotoxin, L-serine-O-sulphate, causes major
disruptions to metabolic pathways in primary cultures of astrocytes.
PMID: 16458390 |
