Armo Hamdoun, Ph.D., Geoffrey Chang, Ph.D.
University of California, San Diego
NIEHS grantees report that environmental pollutants found in fish reduced the effectiveness of the human body’s natural system for expelling harmful contaminants. The new information gained from this study could help improve assessment of human health risks from eating contaminated seafood.
The researchers were interested in finding out how P-glycoprotein (P-gp), a transporter protein that expels foreign chemicals from the body, could rid cells of persistent organic pollutants found in seafood. Persistent organic pollutants are hazardous, man-made chemicals that persist in the environment and bioaccumulate in animals.
The researchers conducted a biochemical analysis to better understand how P-gp proteins from humans and mice interact with persistent organic pollutants most commonly found in people and also detected in the muscle tissues of yellowfin tuna from the Gulf of Mexico. The pollutants included in the study were dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), dichlorodiphenyldichloroethane (DDD), dieldrin, endrin, three forms of polychlorinated biphenyls, and two forms of polybrominated diphenyl ethers, including the common flame retardant PBDE-100.
The researchers found that all ten persistent organic pollutants interfered with the ability of P-gp to clear toxicants from cells. The researchers also solved the structure of P-gp bound to PBDE-100, providing the first view of a pollutant binding to this transporter protein. This structural information could be used to design chemicals with better potential for elimination.
Citation: Nicklisch SC, Rees SD, McGrath AP, Gökirmak T, Bonito LT, Vermeer LM, Cregger C, Loewen G, Sandin S, Chang G, Hamdoun A. 2016. Global marine pollutants inhibit P-glycoprotein: environmental levels, inhibitory effects, and cocrystal structure. Sci Adv 15;2(4):e1600001.