Nutrient deprivation induces the Warburg effect through ROS/AMPK-dependent activation of pyruvate dehydrogenase kinase

摘要: The Warburg effect is known to be crucial for cancer cells acquire energy. Nutrient deficiencies are an important phenomenon in solid tumors, but the on cell metabolism not yet clear. In this study, we demonstrate that starvation of HeLa by incubation with Hank's buffered salt solution (HBSS) induced apoptosis, which was accompanied induction reactive oxygen species (ROS) production and AMP-activated protein kinase (AMPK) phosphorylation. Notably, HBSS increased lactate production, cytoplasmic pyruvate content decreased consumption, failed change dehydrogenase (LDH) activity or glucose uptake. We found rapidly (PDK) activation (PDH) phosphorylation, both were inhibited compound C (an AMPK inhibitor), NAC (a ROS scavenger), dominant negative mutant AMPK. Our data further revealed involvement activation. Moreover, DCA PDK NAC, all significantly starvation-induced enhancement apoptosis. Not only cells, HBSS-induced PDH phosphorylation also observed CL1.5, A431 human umbilical vein endothelial cells. Taken together, first time demonstrated a low-nutrient condition drives utilize glycolysis produce ATP, increases through novel mechanism involving ROS/AMPK-dependent PDK. Such event contributes protecting from apoptosis upon nutrient deprivation.