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.