Ribosomal/Nucleolar Stress Induction Regulates Tert-Butyl Hydroperoxide (tBHP) Mediated Oxidative Stress in Anopheles Gambiae Midguts

<p> <h3> Objective </h3></p><p> A fundamental understanding of redox homeostasis in <em> Anopheles gambiae </em> midgut cells under different oxidative conditions is missing. Such knowledge can aid in the development of new malaria transmission-blocking strategies aimed at disrupting natural homeostatic processes in the mosquito during <em> Plasmodium </em> parasite uptake (i.e. blood feeding). The aim of this study was to understand how the <em> An. gambiae </em> midgut regulates oxidative stress to reactive oxygen species (ROS), especially to a potent ROS-inducer such as tert-Butyl hydroperoxide (tBHP). <h3> Results </h3></p><p> Initial studies using quantitative immunoblot indicated that the expression of the classical antioxidant protein <em> An. gambiae </em> thioredoxin-1 ( <em> Ag </em> Trx-1) remained unchanged across challenges with different concentrations of tBHP suggesting that additional mechanisms to regulate ROS may be involved. We therefore conducted a global proteomic survey, which revealed that <em> An. gambiae </em> midguts under low (50 &mu;M) and high (200 &mu;M) tBHP concentrations were enriched in proteins indicative of ribosomal/nucleolar stress. Ribosomal stress is an inherent cellular response to an imbalance in ribosomal proteins (RPs) due to cellular stress such as oxidative stress. Our data suggest that ribosomal/nucleolar stress is the primary cellular response in <em> An. gambiae </em> midguts under tBHP challenge. Considering these results, we discuss harnessing the ribosomal stress response as a potential malaria transmission-blocking strategy.</p>