Aerobic glycolysis by proliferating cells: a protective strategy against reactive oxygen species 1

Our laboratory has reported that glucose is essential for glycolytic enzyme induction and proliferation of mitogen-activated rat thymocytes (41). Here we show that: 1) Resting thymocytes meet their ATP demand mainly by oxidative glucose breakdown (88%), whereas proliferating thymocytes produce 86% by glycolytic degradation of glucose to lactate and only 14% by oxidation to CO2 and water. 2) In contrast to nonstimulated resting thymocytes, production of PMA primed reactive oxygen species (ROS) in the proliferating cells is nearly abolished. 3) Consistent with this finding, no ROS formation is observed in proliferating human promyelocytic HL-60 cells, whereas differentiated, nonproliferating HL-60 cells exert a marked response upon priming with PMA. 4) The observed reduction of ROS formation by resting thymocytes incubated with pyruvate suggests a function of pyruvate as an H(2)O(2) scavenger. 5) The respiratory chain is a potential origin for ROS because inhibitors of the mitochondrial electron transport strongly reduce H(2)O(2) production by resting thymocytes. The results are discussed in the context of aerobic glycolysis by proliferating cells being a means to minimize oxidative stress during the phases of the cell cycle where maximally enhanced biosynthesis and cell division do occur.