Bcl-2 inhibits tumor necrosis factor-α-mediated increase of glycolytic enzyme activities and enhances pyruvate carboxylase activity

To understand the effects of bcl-2 on glucose metabolism and tumor necrosis factor-α (TNF-α) mediated cytotoxicity, the activities of glycolytic enzymes (hexokinase, 6-phosphofructo-1-kinase, and pyruvate kinase), lactate dehydrogenase, pyruvate carboxylase, and phosphoenolpyruvate carboxykinase were examined with or without TNF-α treatment in TNF-α sensitive L929 cells and TNF-α resistant bcl-2 transfected L929 cells. In TNF-α-treated L929 cells, the activities of the glycolytic enzymes and lactate dehydrogenase greatly increased, but there was no detectable change in phosphoenolpyruvate carboxykinase. Pyruvate carboxylase activity decreased by about 25% between 6 and 12 h after TNF-α treatment. The activities of the glycolytic enzymes and lactate dehydrogenase in bcl-2 transfected L929 cells were lower than in L929 cells upon TNF-α treatment. On the other hand, the activity of pyruvate carboxylase was 20-100% greater after 6 h of TNF-α treatment than in the L929 cells. The activity of phosphoenolpyruvate carboxykinase of bcl-2 trasfected L929 cells was lower by up to 25% than in L929 cells after 12 h. The increase of pyruvate carboxylase activity and decrease of phosphoenolpyruvate carboxykinase activity in bcl-2 transfected L929 cells may contribute to the protective effects of bcl-2 against TNF-α mediated cytotoxicity.