Oxidant-Inducibleadapt15RNA Is Associated with Growth Arrest- and DNA Damage-Induciblegadd153andgadd45

We have recently described a novel RNA, designatedadapt15,which is strongly induced by a pretreatment concentration of hydrogen peroxide in hamster HA-1 fibroblasts under conditions where a protective “adaptive response” occurs.adapt15may therefore be involved in protecting cells against the damaging effects of oxidative stress. Since two other known sequences,gadd45andgadd153,were also found to be induced under our pretreatment conditions and are known to be growth arrest and DNA damage inducible, we decided to also assess the possible association ofadapt15with growth arrest and DNA damage. We found that, likegadd45andgadd153,the levels ofadapt15RNA were low during proliferation, but high during density saturation- and low serum (G0)-growth arrests. Exposure of HA-1 cells to DNA-damaging agents revealed significant induction ofadapt15RNA by methylmethanesulfonate andcis-platinum but not X-irradiation. Near identical responses were also observed forgadd45andgadd153RNAs, suggesting coordinate regulation ofadapt15, gadd45,andgadd153.All three RNAs were also increased relative to control following heat shock, a nongenotoxic treatment. Finally, the induction ofadapt15by hydrogen peroxide was strongly dependent upon calcium, a hallmark ofgadd153induction. The coordinate inductions ofadapt15, gadd45,andgadd153by multiple agents, and their induction by an adaptive- but not by a nonadaptive-response level of hydrogen peroxide, suggest these RNAs may act in concert to protect cells against the damaging effects of oxidative stress.