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

Abstract

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.

The acidic microenvironment as a possible niche of dormant tumor cells

“…Thus, an enhanced lactic acid production during a high rate of proliferation is difficult to imagine, and only when uptake of glucose superimposes anabolic biomass formation, lactic acid starts to accumulate and extracellular pH reduces. A high glycolytic rate has an additional advantage for proliferating tumor cells, that is the reduction of radical oxidative substances and the related cytotoxic effects [14].…”

Energy Management by Enhanced Glycolysis in G1-phase in Human Colon Cancer Cells In Vitro and In Vivo

“…The feature, which has been termed Warburg Effect (1), is observed not only in cancer cells but also in most of proliferating cells (2). An increase in lactate production was found in G 1 phase in HeLa cells (3).…”

Cutting Edge: Hypoxia-Inducible Factor 1α and Its Activation-Inducible Short Isoform I.1 Negatively Regulate Functions of CD4+ and CD8+ T Lymphocytes

“…On the other hand, T cells are not expected to be dependent on HIF-1␣ for survival to the same extent as macrophages since T cells can produce ATP by both glycolysis and oxidative phosphorylation (7). Accordingly, we have proposed that changes in levels of HIF-1␣ may play not only the energy-providing but also a regulatory role in T cell functions in inflamed and hypoxic tissue microenvironments (2).…”