Hachiya, M. and Akashi, M. Catalase Regulates Cell Growth in HL60 Human Promyelocytic Cells: Evidence for Growth Regulation by H2O2. Radiat. Res. 163, 271–282 (2005).
Reactive oxygen species (ROS) including hydrogen peroxide (H2O2) are generated constitutively in mammalian cells. Because of its relatively long life and high permeability across membranes, H2O2 is thought to be an important second messenger. Generation of H2O2 is increased in response to external insults, including radiation. Catalase is located at the peroxisome and scavenges H2O2. In this study, we investigated the role of catalase in cell growth using the H2O2-resistant variant HP100-1 of human promyelocytic HL60 cells. HP100-1 cells had an almost 10-fold higher activity of catalase than HL60 cells without differences in levels of glutathione peroxidase, manganese superoxide dismutase (MnSOD), and copper-zinc SOD (CuZnSOD). HP100-1 cells had higher proliferative activity than HL60 cells. Treatment with catalase or the introduction of catalase cDNA into HL60 cells stimulated cell growth. Exposure of HP100-1 cells to a catalase inhibitor resulted in suppression of cell growth with concomitant increased levels of intracellular H2O2. Moreover, exogenously added H2O2 or depletion of glutathione suppressed cell growth in HL60 cells. Extracellular signal regulated kinase 1/2 (ERK1/2) was constitutively phosphorylated in HP100-1 cells but not in HL60 cells. Inhibition of the ERK1/2 pathway suppressed the growth of HP100-1 cells, but inhibition of p38 mitogen-activated protein kinase (p38MAPK) did not affect growth. Moreover, inhibition of catalase blocked the phosphorylation of ERK1/2 but not of p38MAPK in HP100-1 cells. Thus our results suggest that catalase activates the growth of HL60 cells through dismutation of H2O2, leading to activation of the ERK1/2 pathway; H2O2 is an important regulator of growth in HL60 cells.