Effect of exogenous lactate on rat glioma metabolism.
Glioma-bearing rats were infused intravenously with a solution containing either [3-(13)C]lactate or both glucose and [3-(13)C]lactate for 20 min or 1 hr. Perchloric acid extracts of healthy and tumoral brain tissues were prepared and analyzed by (13)C- and (1)H-observed (13)C-edited nuclear magnetic resonance (NMR) spectroscopy to determine (13)C-label incorporation into brain tissue and glioma metabolites. Moreover, (13)C enrichments in blood lactate and glucose were determined from (1)H-NMR spectra. In the nontumoral tissue, (13)C labeling of amino acids indicated that [3-(13)C]lactate entered the brain and was metabolized. There was no labeling difference between the contralateral and the ipsilateral hemispheres. Lactate metabolism appeared more specifically neuronal, in agreement with our previous results obtained with normal rat brain (Bouzier et al. [2000] J. Neurochem. 75:480-486). In the glioma tissue, comparison of Ala C3, Glu C4, and Gln C4 labeling indicated that the contributions of blood glutamine and tricarboxylic acid (TCA) cycle to glutamate labeling were about 80% and 20%, respectively, after 1 hr of [3-(13)C]lactate infusion. In contrast, these contributions were about 10% and 90%, respectively, when [1-(13)C]glucose was infused in the absence of lactate. This indicated a major effect of the exogenous lactate on glioma metabolism, which may be due to the following process: The high blood lactate level might hinder the drain of glycolytic lactate produced inside the glioma and thus generate a change in redox potential such that the tumor cells are unable to restore it with oxidative phosphorylation. Thereafter, the high NADH level might inhibit glycolysis and the TCA cycle, and glutamine could become the major carbon source for glutamate labeling.
Bouzier-Sore
A K
AK
Unité de Résonance Magnétique des Systèmes Biologiques, UMR 5536, Centre National de la Recherche Scientifique, Université Victor Segalen, Bordeaux, France.
Canioni
P
P
Merle
M
M
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D002244:Carbon / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002952:Citric Acid Cycle / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D005910:Glioma / Q000378:metabolism* / Q000503:physiopathology; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics; D005973:Glutamine / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology; D019344:Lactic Acid / Q000097:blood* / Q000493:pharmacokinetics*; D009682:Magnetic Resonance Spectroscopy; D009243:NAD / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism*
D001786:Blood Glucose; D002250:Carbon Radioisotopes; D005973:Glutamine; D009243:NAD; D019344:Lactic Acid; D002244:Carbon; D005947:Glucose