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Open AccessFeature PaperArticle

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

1
Department of Health and Biomedical Sciences, Nelson Mandela-African Institution of Science and Technology, Tengeru, Arusha 23302, Tanzania
2
W. Harry Feinstone Department of Molecular Microbiology & Immunology & the Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
3
Department of Environmental Health & Ecological Sciences, Ifakara Health Institute, Dar es Salaam 14112, Tanzania
4
Emerging Pathogens Institute, Department of Infectious Diseases & Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA
5
Department of Biology, Loyola University Chicago, Chicago, IL 60660, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Proteomes 2018, 6(4), 47; https://doi.org/10.3390/proteomes6040047
Received: 15 October 2018 / Revised: 7 November 2018 / Accepted: 9 November 2018 / Published: 12 November 2018
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. View Full-Text
Keywords: malaria; Anopheles gambiae; oxidative stress; endoplasmic reticulum stress; paraquat; transmission-blocking malaria; Anopheles gambiae; oxidative stress; endoplasmic reticulum stress; paraquat; transmission-blocking
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Tarimo, B.B.; Law, H.C.H.; Tao, D.; Pastrana-Mena, R.; Kanzok, S.M.; Buza, J.J.; Dinglasan, R.R. Paraquat-Mediated Oxidative Stress in Anopheles gambiae Mosquitoes Is Regulated by An Endoplasmic Reticulum (ER) Stress Response. Proteomes 2018, 6, 47.

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