New perspectives on perfluorochemical ecotoxicology: inhibition and induction of an efflux transporter in the marine mussel, Mytilus californianus.
The toxicological effects of perfluoroalkyl acids on the p-glycoprotein (p-gp) cellular efflux transporter were investigated using the marine mussel Mytilus californianus as a model system. Four of the perfluoroalkyl acids studied exhibit chemosensitizing behavior, significantly inhibiting p-gp transporter activity. The inhibitory potency is maximal for the longer chain acids perfluorononanoate (PFNA) and perfluorodecanoate (PFDA), with average IC50 values of 4.8 and 7.1 microM, respectively. Results indicate that PFNA inhibits p-gp by an indirect mechanism, and this inhibition is reversible and accompanied by a rapid loss of PFNA from the tissue. In addition, PFNA induces expression of the p-gp transporter after a 2-h exposure, a stress response that may result in a metabolic cost to the organism. Given that most organisms, including humans, share efflux transporters as a first line of defense against toxicants, the results of this study may have broader implications for the ecotoxicology of perfluoroalkyl acids.
Stevenson
Charlotte N
CN
Hopkins Marine Station, Stanford University, Pacific Grove, California 93950, USA.
MacManus-Spencer
Laura A
LA
Luckenbach
Till
T
Luthy
Richard G
RG
Epel
David
D
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D000818:Animals; D049872:Bivalvia / Q000187:drug effects*; D004463:Ecology; D005466:Fluorocarbons / Q000633:toxicity*; D008386:Marine Biology
D018435:ATP Binding Cassette Transporter, Subfamily B; D005466:Fluorocarbons