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NMR spectroscopy study of the effect of 3‐nitropropionic acid on glutamate metabolism in cultured astrocytes
Author(s) -
Bakken Inger Johanne,
Johnsen Svein F.,
White Linda R.,
Unsgård Geirmund,
Aasly Jan,
Sonnewald Ursula
Publication year - 1997
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19970315)47:6<642::aid-jnr10>3.0.co;2-x
Subject(s) - glutamine , tricarboxylic acid , glutamate receptor , metabolism , citric acid cycle , astrocyte , biochemistry , glutamic acid , neuroglia , chemistry , biology , amino acid , central nervous system , endocrinology , receptor
3‐Nitropropionic acid (3‐NPA) is a selective and irreversible inhibitor of succinate dehydrogenase. The effect of this compound on the metabolism of [U‐ 13 C]glutamate was studied in astrocytes using 13 C nuclear magnetic resonance spectroscopy. The appearance of [1,2,3‐ 13 C]glutamate in cell extracts and [1,2,3‐ 13 C]glutamine and [U‐ 13 C]lactate in cell media demonstrated the metabolism of labeled glutamate via the tricarboxylic acid cycle. Such labeling was observed in the control situation and also in cells treated with 3 mM 3‐NPA. In the cells treated with 3 mM 3‐NPA, however, the labeling was significantly reduced, and with 10 mM 3‐NPA no such labeling was observed. Labeled aspartate was observed in untreated cells only. Labeled succinate was not detectable under control conditions, but increased dose dependently in the presence of 3‐NPA. Glutamate uptake and conversion of [U‐ 13 C]glutamate to U‐ 13 C]glutamine was largely unaffected by 3‐NPA, and ATP content was unchanged. In a previous study using cerebellar neurons, tricarboxylic acid cycle metabolism was blocked with 3 mM 3‐NPA. The present results show that astrocyte metabolism is more adaptable to blockade of the tricarboxylic acid cycle by 3‐NPA than neuronal metabolism. J. Neurosci. Res. 47:650–654, 1997. © 1997 Wiley‐Liss, Inc.