Type

Journal Article

Authors

Gethin J. McBean
J.Paul G. Malthouse
Chandralal Hewage
Paula M Alves
Lorraine Brennan

Subjects

Pharmacology

Topics
animals newborn nuclear magnetic resonance biomolecular physiology rats analogs derivatives antagonists inhibitors cerebral cortex animals aspartate aminotransferases glucose serine o sulfate chemically induced astrocytes cells cultured neurotoxins carbon radioisotopes energy metabolism alanine drug effects serine central nervous system toxicity alanine transaminase physiopathology lathyrism down regulation rats wistar metabolism glutathione

Impact of the gliotoxin L-serine-O-sulphate on cellular metabolism in cultured rat astrocytes. (2005)

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.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Gethin J. McBean, J.Paul G. Malthouse, Chandralal Hewage, Paula M Alves, Lorraine Brennan

Experts in our system

1
Gethin J. McBean
University College Dublin
Total Publications: 32
 
2
J.Paul G. Malthouse
University College Dublin
Total Publications: 71
 
3
Lorraine Brennan
University College Dublin
Total Publications: 166