Effects of Methionine Sulfoxide Reductase (Msr) in Drosophila

Indianapolis, IN

Anoxia occurs when cells are deprived of oxygen. Drosophila melanogaster (fruit fly) enters a protective coma that allows it to withstand hours of anoxia. The moment of greatest oxidative stress occurs during the period called reoxygenation, When oxygen is reintroduced to the cells, a burst of reactive oxygen species (ROS) causes oxidative damage. Methionine is an amino acid that is most susceptible to oxidation because it is common in proteins. This oxidation is reversible with the methionine sulfoxide reductase (Msr) A and B which reduce the S and R enantiomers, respectively, to functional methionine. Our lab is investigating a link between the Msr genes and anoxia recovery using Drosophila. Our preliminary data indicate that the Msr deficient flies recover longer in comparison to the wildtype flies, containing both Msr genes. For this project, our lab created mutant lines containing either the MsrA or MsrB gene. These mutant lines were aged until they reach senescence. The mutant lines were exposed to one hour of anoxia and their recovery times were recorded through the Drosophila Activity Monitor (DAM). RNA interference (RNAi) was also used to knockdown expression of either Msr genes. Knockdown of either MsrA or MsrB activity throughout all tissues of the animal should mimic the effect of the complete loss-of-function (LOF) deletion mutations. Currently, we have no understanding of how the absence of Msr activity affects the ability of Drosophila to recover from anoxia, especially during aging. Insight on the role of the Msr genes could contribute to a better understanding of how oxidative stress affects anoxia, stroke, and possibly provide information on treating age-related neurodegenerative diseases.