Paraquat-Mediated Oxidative Stress in Anopheles gambiae Mosquitoes Is Regulated by An Endoplasmic Reticulum (ER) Stress Response.

Brian Tarimo,Dingyin Tao,Stefan Kanzok,Joram Buza,Rebecca Pastrana-Mena,Rhoel Dinglasan,Henry Law

doi:10.3390/proteomes6040047

Abstract

Paraquat is a potent superoxide (O2−)-inducing agent that is capable of inducing an oxidative imbalance in the mosquito midgut. This oxidative imbalance can super-stress the malaria parasite, leading to arrested development in the mosquito midgut and reduced transmission. While several studies have explored the effect of paraquat on malaria parasites, a fundamental understanding of the mosquito response to this compound remains unknown. Here, we quantified the mosquito midgut proteomic response to a paraquat-laced sugar meal, and found that An. gambiae midguts were enriched in proteins that are indicative of cells under endoplasmic reticulum (ER) stress. We also carried out qRT-PCR analyses for nine prominent thioredoxin (Trx) and glutathione (GSH)-dependent genes in mosquito midguts post P. falciparum blood meal ingestion to evaluate the concordance between transcripts and proteins under different oxidative stress conditions. Our data revealed an absence of significant upregulation in the Trx and GSH-dependent genes following infected blood meal ingestion. These data suggest that the intrinsic tolerance of the mosquito midgut to paraquat-mediated oxidative stress is through an ER stress response. These data indicate that mosquitoes have at least two divergent pathways of managing the oxidative stress that is induced by exogenous compounds, and outline the potential application of paraquat-like drugs to act selectively against malaria parasite development in mosquito midguts, thereby blocking mosquito-to-human transmission.

Highlights

Malaria caused by the protozoan parasite Plasmodium remains a major global public health problem, despite extensive investment in the control and elimination of this disease
The assumption is that the identified processes would be in addition to those predicted to be mounted by the midgut in order to maintain redox homeostasis during blood feeding and digestion
We have shown that the An. gambiae midgut response to Pqt-mediated oxidative stress initiates an endoplasmic reticulum (ER) stress pathway rather than inducing the canonical Trx or GSH-dependent antioxidant proteins

Summary

Introduction

Malaria caused by the protozoan parasite Plasmodium remains a major global public health problem, despite extensive investment in the control and elimination of this disease. Proteomes 2018, 6, 47 transmission through its insect vector, the Anopheles mosquito. REVIEW meal ingestion by Anopheles mosquitoes, the parasite undergoes an intricate developmental stage in transmission through itsgametocytes insect vector,in thethe. Plasmodium ingested blood fuse and undergo sexual reproduction meal ingestion by Anopheles mosquitoes, the parasite undergoes an intricate developmental stage in form a zygote that shortly thereafter transforms into a motile ookinete. Plasmodium gametocytes in the ingested blood fuse and undergo sexual reproduction blood bolus to invade and traverse the mosquito midgut epithelium to its basal lamina side, where it to form a zygote that shortly thereafter transforms into a motile ookinete. The oocyst grows in size and undergoes sporogony to produce thousands the blood bolus to invade and traverse the mosquito midgut epithelium to its basal lamina side, of sporozoites

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