The effects of altered expression of the Keap1/CncC pathway on the secretion of fluid and salicylate by Malpighian tubules ofDrosophila melanogaster

The Keap1-Nrf2 pathway is a major upstream regulator of xenobiotic detoxification. In Drosophila melanogaster Meigen, targeted expression of Keap1 and CncC (the latter the orthologue of human Nrf2) in the Malpighian (renal) tubules is known to confer resistance to lethal doses of the pesticide malathion, which is metabolized into organic anions. Dietary exposure to organic anions such as salicylate (10 mm) causes increases in the fluid secretion rate and salicylate flux across Malpighian tubules. In the present study, salicylate-selective microelectrodes and Ramsay assays are used to determine the role of Keap1/Nrf2 in regulating these responses. Genetic manipulations designed to increase Nrf2 activity (by knockdown of the repressor Keap1 or overexpression of the Nrf2 coactivator MafS) or to decrease Nrf2 activity (by overexpression of Keap1) are also studied. Although the results of the Keap1 manipulations are inconclusive, there is no increase in the fluid secretion rate or salicylate flux in tubules isolated from flies in which MafS expression is increased.