The Protein Tyrosine Kinase Inhibitor Tyrphostin 23 Strongly Accelerates Glycolytic Lactate Production in Cultured Primary Astrocytes.
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.
Centre for Biomolecular Interactions Bremen, Faculty 2 (Biology/Chemistry), University of Bremen, P.O. Box 330440, 28334, Bremen, Germany.|Centre for Environmental Research and Sustainable Technology, University of Bremen, Bremen, Germany.
Eva-Maria
EM
Blumrich
Centre for Biomolecular Interactions Bremen, Faculty 2 (Biology/Chemistry), University of Bremen, P.O. Box 330440, 28334, Bremen, Germany.
Reshma
R
Kadam
Centre for Biomolecular Interactions Bremen, Faculty 2 (Biology/Chemistry), University of Bremen, P.O. Box 330440, 28334, Bremen, Germany. dringen@uni-bremen.de.|Centre for Environmental Research and Sustainable Technology, University of Bremen, Bremen, Germany. dringen@uni-bremen.de.
Ralf
R
Dringen
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D019344:Lactic Acid / Q000096:biosynthesis*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017208:Rats, Wistar; D020032:Tyrphostins / Q000378:metabolism / Q000494:pharmacology*
D047428:Protein Kinase Inhibitors; D020032:Tyrphostins; D019344:Lactic Acid; D011505:Protein-Tyrosine Kinases; D005947:Glucose; C060641:tyrphostin A23
Glucose; Kinases; Lactate; Tyrphostins; Vanadate