Document Detail

Urate-null rosy mutants of Drosophila melanogaster are hypersensitive to oxygen stress.
MedLine Citation:
PMID:  1316606     Owner:  NLM     Status:  MEDLINE    
It has been proposed that uric acid is an important scavenger of deleterious oxygen radicals in biological systems [Ames, B. N., Cathcart, R., Schwiers, E. & Hochstein, P. (1981) Proc. Natl. Acad. Sci. USA 78, 6858-6852]. We report here an in vivo investigation of the oxygen defense role of uric acid through an analysis of mutants of the rosy (ry) gene of Drosophila melanogaster. The ry gene is the structural gene for the molybdoenzyme, xanthine dehydrogenase; xanthine dehydrogenase-null ry mutants are therefore unable to synthesize urate. The rationale of our approach was to measure the response of urate-null ry mutants to extraordinary oxygen stress as imposed by exposure to radical-generating agents and as conferred by a genetic defect in superoxide dismutase, an established oxygen defense function. We show that urate-null mutants of the ry locus are hypersensitive to paraquat, ionizing radiation, and hyperoxia. Furthermore, compound mutants doubly deficient for uric acid and Cu/Zn-containing superoxide dismutase are synthetic lethals, which are unable to complete metamorphosis under normal growth conditions. These experiments demonstrate unambiguously the importance of urate in oxygen defense in vivo and support our earlier proposal that the molybdoenzyme genetic system plays a critical role in oxygen defense in Drosophila. They also form the basis for our proposal that metamorphosis in Drosophila imposes a crisis of oxygen stress on the developing imago against which uric acid plays an important organ-specific defense. Finally, the results provide a basis for understanding the syndrome of phenotypes, including the hallmark dull brown eye color, which characterizes mutants of this classic genetic system of Drosophila.
A J Hilliker; B Duyf; D Evans; J P Phillips
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  89     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1992 May 
Date Detail:
Created Date:  1992-06-16     Completed Date:  1992-06-16     Revised Date:  2010-09-07    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4343-7     Citation Subset:  IM; S    
Department of Molecular Biology and Genetics, University of Guelph, ON, Canada.
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MeSH Terms
Antioxidants / metabolism*
Crosses, Genetic
Dose-Response Relationship, Radiation
Drosophila melanogaster / drug effects,  genetics*,  physiology
Free Radical Scavengers
Larva / radiation effects
Oxygen / toxicity*
Paraquat / pharmacology
Radiation, Ionizing
Superoxide Dismutase / genetics*
Superoxides / metabolism
Uric Acid / metabolism*
Xanthine Dehydrogenase / genetics*
Reg. No./Substance:
0/Antioxidants; 0/Free Radical Scavengers; 11062-77-4/Superoxides; 4685-14-7/Paraquat; 69-93-2/Uric Acid; 7782-44-7/Oxygen; EC Dismutase; EC Dehydrogenase

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