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Free Radic Biol Med. 2017 Dec;113:323-334. doi: 10.1016/j.freeradbiomed.2017.10.011. Epub 2017 Oct 12.

Metabolomic analysis of oxidative stress: Superoxide dismutase mutation and paraquat induced stress in Drosophila melanogaster.

Author information

1
Department of Chemistry & Biochemistry, Laurentian University, Sudbury, ON, Canada P3E 2C6.
2
Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2.
3
Faculty of Arts & Science - Biology, Nipissing University, North Bay, ON, Canada P1B 8L7.
4
Department of Chemistry & Biochemistry, Laurentian University, Sudbury, ON, Canada P3E 2C6. Electronic address: tmerritt@laurentian.ca.

Abstract

Oxidative stress results in substantial biochemical and physiological perturbations in essentially all organisms. To determine the broad metabolic effects of oxidative stress, we have quantified the response in Drosophila melanogaster to both genetically and environmentally derived oxidative stress. Flies were challenged with loss of Superoxide dismutase activity or chronic or acute exposure to the oxidizing chemical paraquat. Metabolic changes were then quantified using a recently developed chemical isotope labeling (CIL) liquid chromatography - mass spectrometry (LC-MS) platform that targets the carboxylic acid and amine/phenol submetabolomes with high metabolic coverage. We discovered wide spread changes in both submetabolomes in response to all three types of stresses including: changes to the urea cycle, tryptophan metabolism, porphyrin metabolism, as well as a series of metabolic pathways involved in glutathione synthesis. Strikingly, while there are commonalities across the conditions, all three resulted in different metabolomic responses, with the greatest difference between the genetic and environmental responses. Genetic oxidative stress resulted in substantially more widespread effects, both in terms of the percent of the metabolome altered, and the magnitude of changes in individual metabolites. Chronic and acute environmental stress resulted in more similar responses although both were distinct from genetic stress. Overall, these results indicate that the metabolomic response to oxidative stress is complex, reaching across multiple metabolic pathways, with some shared features but with more features unique to different, specific stressors.

KEYWORDS:

Drosophila melanogaster; Liquid chromatography – mass spectrometry; Metabolomics; Paraquat; Superoxide dismutase null allele

[Indexed for MEDLINE]

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