Overexpression of glutathione reductase extends survival in transgenic Drosophila melanogaster under hyperoxia but not normoxia

The purpose of this study was to test the hypothesis that overexpression of glutathione reductase in transgenic Drosophila melanogaster increases resi stance to oxidative stress and retards the aging process. Transgenic flies were generated by microinjection and subsequent mobilization of a P element construct containing the genomic glutathione reductase gene of Drosophila, with 4 kb upstream and 1.5 kb downstream of the coding region. Transgenic animals stably overexpressed glutathione reductase by up to 100% throughout adult life and under continuous exposure to 100% oxygen or air. Under hype roxic conditions, overexpressors had increased longevity, decreased accrual of protein carbonyls, and dramatically increased survival rates after reco very from a semi-lethal dose of 100% oxygen, Under normoxic conditions, ove rexpression of glutathione reductase had no effect on longevity, protein ca rbonyl content, reduced glutathione, or glutathione disulfide content, alth ough the total consumption of oxygen was slightly decreased, Glutathione re ductase activity does not appear to be a rate-limiting factor in anti-aging defenses under normoxic conditions, but it may become a limiting factor wh en the level of oxidative stress is elevated. -Mockett, R. J., Sohal, R. S. , Orr, W. C. Overexpression of glutathione reductase extends survival in tr ansgenic Drosophila melanogaster under hyperoxia but not normoxia.