Abstract
Redox reactions play a central role in the metabolism of an organism. It is vital to maintain redox homeostasis in response to the fluctuation of redox shift in various biological contexts. NADPH-dependent reducing capacity is one of the key factors contributing to the redox homeostasis. To understand the redox capacity and its impact on mosquito fecundity and susceptibility to insecticides in Anopheles gambiae, we examined the dynamics of elevated oxidative state via induction by paraquat (PQ) and the inhibition of NADPH regeneration by 6-aminonicotinamide (6AN). In naïve conditions, inherent oxidative capacity varies between individuals, as measured by GSSG/GSH ratio. The high GSSG/GSH ratio was negatively correlated with fecundity. Both PQ and 6AN feeding increased GSSG/GSH ratio and elevated protein carbonylation, a marker of oxidative damage. Both pro-oxidants lowered egg production. Co-feeding the pro-oxidants with antioxidant lycopene attenuated the adverse effects on fecundity, implying that oxidative stress was the cause of this phenotype. Pre-feeding with 6AN increased insecticide susceptibility in DDT resistant mosquitoes. These results indicate that oxidative state is delicate in mosquitoes, manipulation of NADPH pool may adversely affect fecundity and insecticide detoxification capacity. This knowledge can be exploited to develop novel vector control strategies targeting fecundity and insecticide resistance.
Highlights
Anopheles gambiae is the primary malaria vector in sub-Saharan Africa[1]
The fluxes of glutathione metabolism and elevated GSSG/GSH ratio post blood feeding suggest that redox status fluctuates in the midgut environment during the blood digestion
This system is composed of glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6-PGDH) which act on glucose 6-phosphate and 6-phosphogluconate, respectively, to reduce NADPH from NADP+ (Fig. 2a)
Summary
Anopheles gambiae is the primary malaria vector in sub-Saharan Africa[1]. Vector competence is influenced by many parameters, including fecundity dependent population dynamics such as adult longevity and insecticide resistance[2,3,4,5,6]. Defense against ROS damage utilizes several systems such as thioredoxin reductase, catalase, Cu-Zn SOD, antioxidants and glutathione systems[14]. DeJong et al have shown that ROS detoxification via catalase is crucial for fecundity by protecting the embryo from damage in An. gambiae[18]. These studies indicate that oxidative stress defense at the direct enzymatic level, i.e., catalase, SOD, is essential to fecundity, longevity, and insecticide resistance. These redox reactions require sufficient reducing equivalent NADPH to operate[15]. The vulnerability of NADPH dependent redox homeostasis presents a potential target for vector control
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