Molecular interactions of environmental chemicals with tuna and honeybee xenobiotic defense transporter P-glycoprotein: Using ligand-binding site conservation to predict chemical bioaccumulation
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Molecular interactions of environmental chemicals with tuna and honeybee xenobiotic defense transporter P-glycoprotein: Using ligand-binding site conservation to predict chemical bioaccumulation

Abstract

Environmental chemicals can affect the world’s food quality and quantity in multiple ways. There is increasing evidence for chemical contamination of food and water, such as pesticide residues on fruits or polyfluoroalkyl substances (PFAS) in drinking water. Some of these chemicals can persist in the environment and ultimately bioaccumulate through organism of the terrestrial and aquatic food chains, including fish and other seafood. Other chemicals, such as crop pesticides, can cause collateral or unintended toxicities to non-target organism, including pollinator insects, that are essential workforces for agricultural industries. Yet, the mechanism of chemical bioaccumulation in marine top predators or the (toxic) effects of unintended chemical co-exposures to pollinator insects are still poorly understood.To counteract xenobiotic insults, all living organisms possess a sophisticated cellular defense system consisting of three major mechanisms, including xenobiotic sensors like the aryl hydrocarbon receptor (AhR), detoxifying enzymes like cytochrome P450 (CYP450), and efflux transporters like P-glycoprotein (P-gp). P-glycoprotein (aka MDR1 or ABCB1) is a Multidrug resistance (MDR) transporter ubiquitously expressed in biological barriers, including liver, kidneys, lungs, intestine, brain, and gills. Due to its poly-specific recognition and elimination of xenobiotics, the ABCB1 is considered a key determinant of drug and xenobiotic disposition in all organisms. In this thesis, I seek to explore how environmental chemicals interact with the protective ABCB1 transporter of the apex predator yellowfin tuna and the European honeybee as an agriculturally important pollinator insect. The results of my thesis will provide new avenues to better predict pollutant bioaccumulation in commercial fish species as well as evaluate and mitigate potentially toxic mixture effects of crop pesticides and in-hive medicines to honeybees.

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