Abstract:
: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.
journal_name
Neurochem Intjournal_title
Neurochemistry internationalauthors
Brennan L,Alves PM,Hewage C,Malthouse JP,McBean GJdoi
10.1016/j.neuint.2005.12.004subject
Has Abstractpub_date
2006-06-01 00:00:00pages
739-45issue
8eissn
0197-0186issn
1872-9754pii
S0197-0186(06)00014-3journal_volume
48pub_type
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