AEROBIC GLYCOLYSIS BY PROLIFERATING CELLS - PROTECTION AGAINST OXIDATIVE STRESS AT THE EXPENSE OF ENERGY YIELD

Primary cultures of mitogen-activated rat thymocytes were used to stud y energy metabolism, gene expression of glycolytic enzymes, and produc tion of reactive oxygen species during cell cycle progression. During transition from the resting to the proliferating state a 7- to 10-fold increase of glycolytic enzyme induction occurs which enables the cell s to meet the enhanced energy demand by increased aerobic glycolysis. Cellular redox changes have been found to regulate gene expression of glycolytic enzymes by reversible oxidative inactivation of Spl-binding to the cognate DNA-binding sites in the promoter region. In contrast to nonproliferating cells, production of phorbol 12-myristate 13-aceta te (PMA)-primed reactive oxygen species (ROS) in proliferating rat thy mocytes and HL-60 cells is nearly abolished. Pyruvate, a product of ae robic glycolysis, is an effective scavenger of ROS, which could be sho wn to be generated mainly at the site of complex III of the mitochondr ial respiratory chain. Aerobic glycolysis by proliferating cells is di scussed as a means to minimize oxidative stress during the phases of t he cell cycle when maximally enhanced biosynthesis and cell division d o occur.