Hamsteradapt78mRNA Is a Down Syndrome Critical Region Homologue That Is Inducible by Oxidative Stress

We are using the technique of mRNA differential display to identify RNAs that may be important in protecting cells against the damaging effects of oxidative stress. For these studies, we utilize a so-called “adaptive response” model system in which hamster HA-1 cells respond to a minimally toxic “pretreatment” dose of hydrogen peroxide by synthesizing RNAs and proteins that protect them against subsequent exposure to a highly cytotoxic concentration of hydrogen peroxide. Using this approach, we have recently reported several novel RNAs whose levels are increased under conditions of adaptive response. Here we report a new RNA, designatedadapt78,whose steady-state level is significantly induced by a pretreatment dose of hydrogen peroxide.adapt78mRNA was calculated to be 2.35 kb in size and inducible by the standard pretreatment dose of 4 μmol H2O2/107cells. It was induced as early as 90 min after peroxide exposure and maximally at 5 h. Induction was strongly dependent upon calcium. Cloning and sequencing revealed a large predicted open reading frame of 197 amino acids.In vitrotranscription and translation generated a protein of 25,000 Da. GenBank homology analysis revealed that much ofadapt78is strongly homologous to a sequence that has been mapped to the Down syndrome critical region (Fuenteset al., Hum. Mol. Genet.4, 1935–1944, 1995). However, both the 5′ and the 3′ ends ofadapt78show no homology to any previously reported complete sequence.adapt78represents a new oxidant-inducible RNA and marker of cellular oxidative stress and may provide new insight into our understanding of oxidant-related disorders and neural degeneration.