Analyses of Fruit Flies That Do Not Express Selenoproteins or Express the Mouse Selenoprotein, Methionine Sulfoxide Reductase B1, Reveal a Role of Selenoproteins in Stress Resistance

Authors

Valentina A. Shchedrina, University of Nebraska - LincolnFollow
Hadise Kabil, University of Nebraska - Lincoln
Gerd Vorbruggen, Max-Planck-Institut fur biophysikalische Chemie, Gottingen
Byung Cheon Lee, Brigham and Women’s Hospital and Harvard Medical SchoolFollow
Anton A. Turanov, University of Nebraska - LincolnFollow
Mitsuko Hirosawa- Takamori, Max-Planck-Institut fur biophysikalische Chemie, Gottingen
Hwa- Young Kim, Yeungnam University College of Medicine
Lawrence G. Harshman, University of Nebraska - LincolnFollow
Dolph L. Hatfield, National Cancer Institute, National Institutes of Health, Bethesda, MDFollow
Vadim N. Gladyshev, Harvard Medical SchoolFollow

Document Type

Article

Date of this Version

2011

Citation

J. Biol. Chem. 2011, 286:29449-29461.

doi: 10.1074/jbc.M111.257600 originally published online May 27, 2011

Comments

US government work

Abstract

Selenoproteins are essential in vertebrates because of their crucial role in cellular redox homeostasis, but some invertebrates that lack selenoproteins have recently been identified. Genetic disruption of selenoprotein biosynthesis had no effect on lifespan and oxidative stress resistance of Drosophila melanogaster. In the current study, fruit flies with knock-out of the selenocysteine-specific elongation factor were metabolically labeled with ⁷⁵Se; they did not incorporate selenium into proteins and had the same lifespan on a chemically defined diet with or without selenium supplementation. These flies were, however, more susceptible to starvation than controls, and this effect could be ascribed to the function of selenoprotein K. We further expressed mouse methionine sulfoxide reductase B1 (MsrB1), a selenoenzyme that catalyzes the reduction of oxidized methionine residues and has protein repair function, in the whole body or the nervous system of fruit flies. This exogenous selenoprotein could only be expressed when the Drosophila selenocysteine insertion sequence element was used, whereas the corresponding mouse element did not support selenoprotein synthesis. Ectopic expression of MsrB1 in the nervous system led to an increase in the resistance against oxidative stress and starvation, but did not affect lifespan and reproduction, whereas ubiquitous MsrB1 expression had no effect. Dietary selenium did not influence lifespan of MsrB1-expressing flies. Thus, in contrast to vertebrates, fruit flies preserve only three selenoproteins, which are not essential and play a role only under certain stress conditions, thereby limiting the use of the micronutrient selenium by these organisms.