Abstract
We have previously discovered that the adult Drosophila melanogaster is tolerant to a low O2 environment, withstanding hours of total O2 deprivation without showing any evidence of cell injury. Subsequently, our laboratory embarked on the study of hypoxia tolerance using a mutagenesis and overexpression screens to begin to investigate loss-of-function or gain-of-function phenotypes. Both have given us promising results and, in this article, we detail some of the interesting results. Furthermore, several years ago, we have also started an experimental “Darwinian” selection to generate a fly strain that can perpetuate through all of its life cycle stages in hypoxic environments. Through microarrays and bioinformatic analyses, we have obtained genes (e.g. Notch pathway genes) that play an important role in hypoxia resistance. In addition, we also detail a proof of principle that Drosophila genes that are beneficial in fly resistance to hypoxia can also be as well in mammalian cells. We believe that the mechanisms that we are uncovering in Drosophila will allow us to gain insight regarding susceptibility and tolerance to low O2 and will therefore pave the way to develop better therapies for ailments that afflict humans as a consequence of low O2 delivery or low blood O2 levels.
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Abbreviations
- AF:
-
hypoxia-adapted/selected flies
- CH:
-
constant hypoxia
- dADAR:
-
pre-mRNA adenosine deaminase
- dMRP4:
-
Drosophila homolog of the human multidrug resistance protein 4
- IH:
-
intermittent hypoxia
- NF:
-
naïve control flies
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Supported by the Grants NIH P01 HD 32573 and NIH R01 NS 037756 from the National Institutes of Health (to G.G.H) and the Grant AHA 0835188N from the American Heart Association (to D.Z.).
The Role of Oxygen in Health and Disease - A Series of Reviews
This is the fifth and last article in the series of reviews focusing on the role that oxygen plays in health and disease. As a proof of principle, Drs. Zhou, Visk and Haddad have described Drosophila genes, beneficial in developing resistance to hypoxia, to provide insight regarding susceptibility and tolerance to low oxygen. This information will pave the way towards developing improved therapies for mammalian species to combat the consequences of low oxygen delviery and low blood oxygen levels.
Sherin U. Devaskar, M.D.
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Zhou, D., Visk, D. & Haddad, G. Drosophila, a Golden Bug, for the Dissection of the Genetic Basis of Tolerance and Susceptibility to Hypoxia. Pediatr Res 66, 239–247 (2009). https://doi.org/10.1203/PDR.0b013e3181b27275
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DOI: https://doi.org/10.1203/PDR.0b013e3181b27275
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