NMR spectroscopy study of the effect of 3-nitropropionic acid on glutamate metabolism in cultured astrocytes

✍ Scribed by Inger Johanne Bakken; Svein F. Johnsen; Linda R. White; Geirmund Unsgård; Jan Aasly; Ursula Sonnewald

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 113 KB
• Volume: 47
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/(sici)1097-4547(19970315)47:6<642::aid-jnr10>3.0.co;2-x

✦ Synopsis

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.