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Neurochemical Research

, Volume 41, Issue 10, pp 2607–2618 | Cite as

The Protein Tyrosine Kinase Inhibitor Tyrphostin 23 Strongly Accelerates Glycolytic Lactate Production in Cultured Primary Astrocytes

  • Eva-Maria Blumrich
  • Reshma Kadam
  • Ralf Dringen
Original Paper

Abstract

Tyrphostin 23 (T23) is a well-known inhibitor of protein tyrosine kinases. To investigate potential acute effects of T23 on the viability and the glucose metabolism of brain cells, we exposed cultured primary rat astrocytes to T23 for up to 4 h. While the viability and the morphology of the cultured astrocytes were not acutely affected by the presence of T23 in concentrations of up to 300 µM, this compound caused a rapid, time- and concentration-dependent increase in glucose consumption and lactate release. Maximal effects on glycolytic flux were found for incubations with 100 µM T23 for 2 h which doubled both glucose consumption and lactate production. The stimulation of glycolytic flux by T23 was reversible, completely abolished upon removal of the compound and not found in presence of other known inhibitors of endocytosis. Structurally related compounds such as tyrphostin 25 and catechol or modulators of AMP kinase activity did neither affect the basal nor the T23-stimulated lactate production by astrocytes. In contrast, the presence of the phosphatase inhibitor vanadate completely abolished the stimulation by T23 of astrocytic lactate production in a concentration-dependent manner. These data suggest that T23-sensitive phosphorylation/dephosphorylation events are involved in the regulation of astrocytic glycolysis.

Keywords

Glucose Kinases Lactate Tyrphostins Vanadate 

Notes

Acknowledgments

The authors would like to thank Yvonne Koehler (University of Bremen) for her support in establishing the assay to determine intracellular glucose and Prof. Dr. Soerge Kelm (University of Bremen) for providing access to his fluorescence microtiter plate reader.

Compliance with Ethical Standards

Conflict of Interest

The authors have no conflict of interest to declare.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Eva-Maria Blumrich
    • 1
    • 2
  • Reshma Kadam
    • 1
  • Ralf Dringen
    • 1
    • 2
  1. 1.Centre for Biomolecular Interactions Bremen, Faculty 2 (Biology/Chemistry)University of BremenBremenGermany
  2. 2.Centre for Environmental Research and Sustainable TechnologyUniversity of BremenBremenGermany

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