engleski

Multidrug efflux transporters limit accumulation of inorganic, but not organic, mercury in sea urchin embryos

In this study we examined the role of multidrug efflux transport in differential accumulation and potency of inorganic (HgCl2) and organic (CH3HgCl) mercury in sea urchin (Strongylocentrotus purpuratus) embryos. To quantify mercury toxicity we assessed the effect of HgCl2 and CH3HgCl on cell division. Our assay detects the incidence of interference with progression through the first cell cycle, which occurs primarily through the effects of mercury on spindles (microtubules) in metaphase and anaphase. We found that the EC50 concentrations for interference with mitosis are 610 nM for HgCl2 and 124 nM for CH3HgCl. Pharmacological inhibition of MRP/ABCC-type multidrug efflux activity significantly increases the anti-mitotic potency of inorganic mercury, but has virtually no effect on the potency of organic mercury - partial inhibition of the MRP mediated efflux activity with 5 µM MK571, a model inhibitor of MRP efflux transporters, increased the toxicity of HgCl2 2.8-fold. Similarly, inhibition of these transporters increased intracellular accumulation of HgCl2 but has no effect on accumulation on CH3HgCl – 5 µM MK571 caused 2-fold and 20 µM MK571 caused 4-fold increase in intracellular mercury accumulation. Our results point to the MRP mediated efflux transport as an important biological determinant of mercury accumulation and subsequent toxic potency in aquatic organisms.

multidrug efflux transport; inorganic (HgCl2) mercury; organic (CH3HgCl) mercury; sea urchin (Strongylocentrotus purpuratus) embryos

nije evidentirano