The tricarboxylic acid cycle activity in cultured primary astrocytes is strongly accelerated by the protein tyrosine kinase inhibitor tyrphostin 23

Tyrphostin 23 (T23) is a well-known inhibitor of protein tyrosine kinases and has been considered as potential anti-cancer drug. T23 was recently reported to acutely stimulate the glycolytic flux in primary cultured astrocytes. To investigate whether T23 also affects the tricarboxylic acid (TCA) cyc...

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Bibliographic Details
Published in:Neurochemistry international 2017-01, Vol.102, p.13-21
Main Authors: Hohnholt, Michaela C., Blumrich, Eva-Maria, Waagepetersen, Helle S., Dringen, Ralf
Format: Article
Language:English
Subjects:
Animals
Aspartic Acid - metabolism
Astrocytes
Astrocytes - drug effects
Astrocytes - metabolism
Cells, Cultured
Citric Acid Cycle - drug effects
Glucose - metabolism
Glutamic Acid - metabolism
Glycolysis - drug effects
Glycolysis - physiology
Lactate
Metabolism
Protein Kinase Inhibitors - pharmacology
Rats, Wistar
Tricarboxylic acid cycle
Tyrphostins
Tyrphostins - pharmacology
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Summary:Tyrphostin 23 (T23) is a well-known inhibitor of protein tyrosine kinases and has been considered as potential anti-cancer drug. T23 was recently reported to acutely stimulate the glycolytic flux in primary cultured astrocytes. To investigate whether T23 also affects the tricarboxylic acid (TCA) cycle, we incubated primary rat astrocyte cultures with [U-13C]glucose in the absence or the presence of 100 μM T23 for 2 h and analyzed the 13C metabolite pattern. These incubation conditions did not compromise cell viability and confirmed that the presence of T23 doubled glycolytic lactate production. In addition, T23-treatment strongly increased the molecular carbon labeling of the TCA cycle intermediates citrate, succinate, fumarate and malate, and significantly increased the incorporation of 13C-labelling into the amino acids glutamate, glutamine and aspartate. These results clearly demonstrate that, in addition to glycolysis, also the mitochondrial TCA cycle is strongly accelerated after exposure of astrocytes to T23, suggesting that a protein tyrosine kinase may be involved in the regulation of the TCA cycle in astrocytes. •T23 stimulates glycolytic flux in cultured astrocytes.•Molecular carbon labeling from [U-13C]glucose is enhanced in tricarboxylic acid cycle intermediates.•Mitochondrial metabolism of brain astrocytes is accelerated by T23 exposure.
ISSN:0197-0186
1872-9754
DOI:10.1016/j.neuint.2016.11.008