title: Hamster adapt78 mRNA is a Down syndrome critical region homologue that is inducible by oxidative stress.
abstract: 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, designated adapt78, whose steady-state level is significantly induced by a pretreatment dose of hydrogen peroxide. adapt78 mRNA was calculated to be 2.35 kb in size and inducible by the standard pretreatment dose of 4 micromol H2O2/10(7) cells. 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 vitro transcription and translation generated a protein of 25,000 Da. GenBank homology analysis revealed that much of adapt78 is strongly homologous to a sequence that has been mapped to the Down syndrome critical region (Fuentes et al., Hum. Mol. Genet. 4, 1935-1944, 1995). However, both the 5' and the 3' ends of adapt78 show no homology to any previously reported complete sequence. adapt78 represents 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, The Albany Medical College, New York 12208, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Crawford
authors.forename: K P
authors.initials: KP
authors.lastname: Leahy
authors.forename: N
authors.initials: N
authors.lastname: Abramova
authors.forename: L
authors.initials: L
authors.lastname: Lan
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: K J
authors.initials: KJ
authors.lastname: Davies
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D006224:Cricetinae; D018076:DNA, Complementary / Q000737:chemistry; D004314:Down Syndrome / Q000235:genetics*; D006861:Hydrogen Peroxide; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D018076:DNA, Complementary; D012333:RNA, Messenger; D006861:Hydrogen Peroxide; D002118:Calcium