title: Experimental selection for Drosophila survival in extremely high O2 environments.
abstract: Although oxidative stress is deleterious to mammals, the mechanisms underlying oxidant susceptibility or tolerance remain to be elucidated. In this study, through a long-term laboratory selection over many generations, we generated a Drosophila melanogaster strain that can live and reproduce in very high O(2) environments (90% O(2)), a lethal condition to naïve flies. We demonstrated that tolerance to hyperoxia was heritable in these flies and that these hyperoxia-selected flies exhibited phenotypic differences from naïve flies, such as a larger body size and increased weight by 20%. Gene expression profiling revealed that 227 genes were significantly altered in expression and two third of these genes were down-regulated. Using a mutant screen strategy, we studied the role of some altered genes (up- or down-regulated in the microarrays) by testing the survival of available corresponding P-element or UAS construct lines under hyperoxic conditions. We report that down-regulation of several candidate genes including Tropomyosin 1, Glycerol 3 phosphate dehydrogenase, CG33129, and UGP as well as up-regulation of Diptericin and Attacin conferred tolerance to severe hyperoxia. In conclusion, we identified several genes that were not only altered in hyperoxia-selected flies but we also prove that these play an important role in hyperoxia survival. Thus our study provides a molecular basis for understanding the mechanisms of hyperoxia tolerance.
authors.affiliation: Division of Respiratory Medicine, Department of Pediatrics, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Huiwen W
authors.initials: HW
authors.lastname: Zhao
authors.forename: Dan
authors.initials: D
authors.lastname: Zhou
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
authors.forename: Gabriel G
authors.initials: GG
authors.lastname: Haddad
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D005993:Glycerolphosphate Dehydrogenase / Q000235:genetics; D018496:Hyperoxia / Q000503:physiopathology; D053208:Kaplan-Meier Estimate; D020411:Oligonucleotide Array Sequence Analysis; D010100:Oxygen / Q000494:pharmacology*; D012098:Reproduction / Q000187:drug effects / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014335:Tropomyosin / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; C490776:Tm1 protein, Drosophila; D014335:Tropomyosin; D005993:Glycerolphosphate Dehydrogenase; D010100:Oxygen