NMR spectroscopy study of the effect of 3-nitropropionic acid on glutamate metabolism in cultured astrocytes.
3-Nitropropionic acid (3-NPA) is a selective and irreversible inhibitor of succinate dehydrogenase. The effect of this compound on the metabolism of [U-13C]glutamate was studied in astrocytes using 13C nuclear magnetic resonance spectroscopy. The appearance of [1,2,3-13C]glutamate in cell extracts and [1,2,3-13C]glutamine and [U-13C]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-13C]glutamate to [U-13C]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.
Bakken
I J
IJ
Department of Physics, Norwegian University of Science and Technology, Trondheim.
Johnsen
S F
SF
White
L R
LR
Unsgård
G
G
Aasly
J
J
Sonnewald
U
U
D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002247:Carbon Isotopes; D018698:Glutamic Acid / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D009498:Neurotoxins / Q000494:pharmacology; D009574:Nitro Compounds; D017397:Prefrontal Cortex / Q000166:cytology / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology*; D013386:Succinates / Q000378:metabolism
D002247:Carbon Isotopes; D007773:Lactates; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D013386:Succinates; D001224:Aspartic Acid; D018698:Glutamic Acid; C015392:3-nitropropionic acid