ACTIVATION OF DNA-SYNTHESIS AND EXPRESSION OF THE JE GENE BY CATALASEIN MOUSE OSTEOBLASTIC CELLS - POSSIBLE INVOLVEMENT OF HYDROGEN-PEROXIDE IN NEGATIVE GROWTH-REGULATION

The addition of catalase isolated from bovine liver to the culture med ium of quiescent mouse osteoblastic MC3T3-E1 cells decreased intracell ular oxidized state, determined using fluorescent dye and laser-scanni ng confocal microscopy. The decrease in intracellular oxidized state e voked by catalase seemed to be involved in the arrest of growth, since catalase increased the incorporation of [H-3]thymidine in these quies cent cells. On gel filtration of the catalase preparation, catalase ac tivity and the stimulation of DNA synthesis coincided. Of the early re sponse genes, JE, which is induced by competence factors, was induced by catalase in this cell line, whereas c-fos, c-jun, and KC mRNA level s were not affected. Catalase isolated from fungi and glutathione pero xidase + glutathione added to the culture medium also increased the st eady-state level of JE mRNA. These results indicate that cells in the quiescent state produce hydrogen peroxide endogenously and that hydrog en peroxide acts as one of the mediators inhibiting DNA synthesis as w ell as the expression of JE, a growth factor-inducible gene. (C) 1995 Academic Press, Inc.