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

Abstract The K eap1‐ N rf2 pathway is a major upstream regulator of xenobiotic detoxification. In D rosophila melanogaster M eigen, targeted expression of K eap1 and CncC (the latter the orthologue of human N rf2) in the M alpighian (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 m m ) causes increases in the fluid secretion rate and salicylate flux across M alpighian tubules. In the present study, salicylate‐selective microelectrodes and R amsay assays are used to determine the role of K eap1/ N rf2 in regulating these responses. Genetic manipulations designed to increase N rf2 activity (by knockdown of the repressor K eap1 or overexpression of the N rf2 coactivator MafS ) or to decrease N rf2 activity (by overexpression of K eap1) are also studied. Although the results of the K eap1 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.