Dataset Information

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

ABSTRACT: Paraquat is a potent superoxide (O?-)-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.

SUBMITTER: Tarimo BB

PROVIDER: S-EPMC6313908 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Tarimo Brian B BB Law Henry Chun Hin HCH Tao Dingyin D Pastrana-Mena Rebecca R Kanzok Stefan M SM Buza Joram J JJ Dinglasan Rhoel R RR

Proteomes 20181112 4

Paraquat is a potent superoxide (O₂<sup>-</sup>)-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 proteomi ...[more]

PMID: 30424486

Similar Datasets

Project description:A deeper understanding of malaria parasite development inside the Anopheles mosquito may lead to the identification of processes that can be targeted by transmission-blocking interventions. Paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride) is a potent superoxide-inducing agent that impacts Plasmodium ookinete development, especially at higher concentrations. Compounds like Paraquat can potentially induce an oxidative imbalance in the mosquito midgut during ookinete maturation, essentially super-stressing the parasite leading to the arrested development of ookinetes, the only stage that can invade through a mosquito midgut cell to establish an oocyst infection in the mosquito. The mosquito midgut has evolved to handle the natural production of reactive oxygen and nitrogen species (ROS and RNS, respectively) as a result of feeding on blood. The addition of Paraquat to a bloodmeal is expected to induce a cognate response in the midgut to handle the excess ROS/RNS, and high concentrations of this compound can potentially overwhelm the midgut response leading to mosquito death. 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 to understand the intrinsic midgut response (in the absence of a bloodmeal). We then carried out transcriptomic analysis of the mosquito midgut for several antioxidants of the Trx and GSH pathways to compare concordance or discordance between protein and its transcripts during different oxidative stress conditions. Finally, we determined whether the same Trx and GSH pathways are upregulated following infection with either P. falciparum or P. berghei at 24 hrs post-blood feeding, coinciding with the time point for maximal ookinete traversal of the midgut. We discuss the potential selective action of Paraquat on the parasite and the intrinsic tolerance of the mosquito midgut to Paraquat-mediated oxidative stress.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets