Document Detail

An NMR study of alterations in [1-13C]glucose metabolism in C6 glioma cells by gliotoxic amino acids.
MedLine Citation:
PMID:  12547642     Owner:  NLM     Status:  MEDLINE    
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.
Lorraine Brennan; Chandralal Hewage; J Paul G Malthouse; Gethin J McBean
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neurochemistry international     Volume:  42     ISSN:  0197-0186     ISO Abbreviation:  Neurochem. Int.     Publication Date:  2003 May 
Date Detail:
Created Date:  2003-01-27     Completed Date:  2003-05-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8006959     Medline TA:  Neurochem Int     Country:  England    
Other Details:
Languages:  eng     Pagination:  441-8     Citation Subset:  IM    
Department of Biochemistry, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
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MeSH Terms
Amino Acids / metabolism*
Brain Neoplasms / metabolism*,  pathology
Carbon Isotopes / metabolism
Glioma / metabolism*,  pathology
Glucose / metabolism*
Magnetic Resonance Spectroscopy
Tumor Cells, Cultured
Reg. No./Substance:
0/Amino Acids; 0/Carbon Isotopes; 50-99-7/Glucose

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