Regulation of oxidative stress responses in the malaria vector, Anopheles stephensi

Reactive oxygen species (ROS) are oxygen-based free radicals normally produced by electrons leaked from the electron transport chain during aerobic metabolism. Because ROS are highly reactive and can damage cell membranes, DNA, and proteins, cells have a tightly-regulated response mechanism to relieve states of elevated ROS concentrations (oxidative stress). Two major protein regulators in this mechanism are Nrf2, a transcription factor that binds to the antioxidant response element (ARE) region of antioxidant genes’ promoters, and Keap1, its oxidative stress-sensitive repressor. In mosquitoes, and blood-feeding insects in general, digestion of the blood meal produces an unusually high ROS burden on the organism because of the production of free radicals in the midgut lumen by heme groups. It is therefore particularly important for mosquitoes to have strong midgut antioxidant defenses during and after a blood meal. In this study, we examined the role Nrf2 and Keap1 have in responding to oxidative stress caused by blood meal ingestion and whether knockdown of Nrf2 can inhibit the upregulation of antioxidant enzymes such as catalase and superoxide dismutase.