Activation of DNA synthesis and expression of the JE gene by catalase in mouse osteoblastic cells: possible involvement of hydrogen peroxide in negative growth regulation.

The addition of catalase isolated from bovine liver to the culture medium of quiescent mouse osteoblastic MC3T3-E1 cells decreased intracellular oxidized state, determined using fluorescent dye and laser-scanning confocal microscopy. The decrease in intracellular oxidized state evoked by catalase seemed to be involved in the arrest of growth, since catalase increased the incorporation of [3H]thymidine in these quiescent cells. On gel filtration of the catalase preparation, catalase activity and the stimulation of DNA synthesis coincided. Of the early response genes, JE, which is induced by competence factors, was induced by catalase in this cell line, whereas c-fos, c-jun, and KC mRNA levels were not affected. Catalase isolated from fungi and glutathione peroxidase+glutathione added to the culture medium also increased the steady-state level of JE mRNA. These results indicate that cells in the quiescent state produce hydrogen peroxide endogenously and that hydrogen peroxide acts as one of the mediators inhibiting DNA synthesis as well as the expression of JE, a growth factor-inducible gene.