Type

Journal Article

Authors

Gethin J. McBean
J.Paul G. Malthouse
Chandralal Hewage
Lorraine Brennan

Subjects

Biochemistry

Topics
tumor cells cultured amino acids glucose glioma pathology humans metabolism carbon isotopes magnetic resonance spectroscopy brain neoplasms

An NMR study of alterations in [1-13C]glucose metabolism in C6 glioma cells by gliotoxic amino acids. (2003)

Abstract A series of glutamate analogues, known as gliotoxins, are toxic to astrocytes in culture, and are inhibitors or substrates of high affinity sodium-dependent glutamate transporters. The mechanisms by which these gliotoxins cause toxicity are not fully understood. The effects of a series of gliotoxic amino acids (L-alpha-aminoadipate, L-serine-O-sulphate, D-aspartate and L-cysteate) on metabolism of [1-13C]glucose were examined in C6 glioma cells using 13C nuclear magnetic resonance (NMR) spectroscopy. The cells were preincubated in the presence of sub toxic concentrations of each gliotoxin (400 micromol/l) for 20 h. This was followed by incubation (4 h) with [1-13C]glucose (5.5 mmol/l) in the presence and absence of each gliotoxin. The incorporation of 13C label into the observed metabolites was analysed. Following preincubation with L-alpha-aminoadipate, D-aspartate, and L-serine-O-sulphate there was a significant decrease in the incorporation of 13C label into glutamate, alanine and lactate from [1-13C]glucose. In the presence of L-cysteate production of labelled glutamate was decreased, while there was no significant effect on the concentrations of labelled lactate and alanine. There was no change in the quantity of LDH released into the medium after incubation of the cells with any of the gliotoxins. Overall these results indicate that the presence of gliotoxins profoundly alters the flux of glucose to lactate, alanine, aspartate and glutamate.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Gethin J. McBean, J.Paul G. Malthouse, Chandralal Hewage, 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