The world’s oceans are a global reservoir of
persistent organic pollutants to which humans and
other animals are exposed. Although it is well known
that these pollutants are potentially hazardous to
human and environmental health, their impacts remain
( Thunnus albacares ). Gulf of
Mexico. SEFSC Pascagoula Laboratory; Collection of
Brandi Noble, NOAA/NMFS/SEFSC.
Researchers examined how
persistent organic pollutants interact with the drug
efflux transporter P-glycoprotein (P-gp), an
evolutionarily conserved defense protein that is
essential for protection against environmental
They identified specific congeners of organochlorine
pesticides, polychlorinated biphenyls, and
polybrominated diphenyl ethers that inhibit mouse
and human P-gp, and determined their environmental
levels in yellowfin tuna from the Gulf of Mexico.
In addition, scientists
solved the cocrystal structure of P-gp bound to one
of these inhibitory pollutants, PBDE (polybrominated
diphenyl ether)–100, providing the first view of
pollutant binding to a drug transporter.
The results demonstrate
the potential for specific binding and inhibition of
mammalian P-gp by ubiquitous congeners of persistent
organic pollutants present in fish and other foods,
and argue for further consideration of transporter
inhibition in the assessment of the risk of exposure
to these chemicals.
For more information
Global marine pollutants inhibit P-glycoprotein:
Environmental levels, inhibitory effects, and
Sascha C. T. Nicklisch, Steven D. Rees, Aaron P.
McGrath, Tufan Gökirmak, Lindsay T. Bonito, Lydia M.
Vermeer, Cristina Cregger, Greg Loewen, Stuart
Sandin, Geoffrey Chang and Amro Hamdoun
Scripps Institution of Oceanography, UC San Diego