Antioxidant function of a novel selenoprotein in Drosophila melanogaster.
BACKGROUND
Insects appear to have diverged from both higher and lower organisms in their defense mechanisms against oxidative damage. They do not encode glutathione peroxidases or glutathione reductases, and their thioredoxin reductases exhibit distinct properties from those of higher and lower species. Nonetheless, appropriate balance of anti-oxidants and pro-oxidants, and protection from damaging reactive oxygen species are clearly crucial in insects for viability, normal functioning of signalling pathways and morphogenesis, and have been implicated in studies on longevity in flies and other organisms.


RESULTS
Two novel selenoproteins, dselH and dselK, were recently identified in Drosophila melanogaster. We have used RNAi in D. melanogaster embryos and in Schneider S2 cells to inhibit expression of these proteins. We report that inhibition of either dselH or dselK expression significantly reduces viability in embryos. We further show that dselH silencing decreases total anti-oxidant capacity in embryos and Schneider cells, and increases lipid peroxidation in cells. Conversely, transient expression of dselH in the cell line decreases lipid peroxidation, and reverses the toxic effects of a glutathione-depleting drug. The latter correlates with sparing of glutathione levels.


CONCLUSIONS
These studies suggest that the well-known role of selenoproteins in vertebrate anti-oxidant defenses also extends to include invertebrates.
Morozova
Nadya
N
Thyroid Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Forry
Erin P
EP
Shahid
Elena
E
Zavacki
Ann Marie
AM
Harney
John W
JW
Kraytsberg
Yevgenya
Y
Berry
Marla J
MJ
D000818:Animals; D000975:Antioxidants / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival; D019610:Cytoprotection; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D005314:Embryonic and Fetal Development; D005978:Glutathione / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D018384:Oxidative Stress; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D051140:Selenoproteins
D000975:Antioxidants; C490438:BthD protein, Drosophila; D029721:Drosophila Proteins; D008565:Membrane Proteins; D011506:Proteins; C490437:SelG protein, Drosophila; D051140:Selenoproteins; D005978:Glutathione