engleski

Multidrug resistance-associated protein (MRP) protects sea urchin embryos (Strongylocentrotus purpuratus) against mercuric chloride

Multidrug resistance-associated proteins (MRPs), or ATP-Binding Cassette C (ABCC) family transporters, are unique from other multidrug transporters in that they efflux both organics and heavy metal mercaptide complexes. To investigate the protective capacity of these transporters from mercury, a pollutant of major concern in marine environments, we examined the effects of mercuric chloride on sea urchin (Strongylocentrotus purpuratus) embryos, which have high levels of ABCC/MRP efflux activity. We found that mercuric chloride interferes with mitosis (EC50 837 nM) by inducing breakage of astral microtubules, thereby retarding or blocking metaphase and anaphase. Partial inhibition of the ABCC/MRP mediated efflux activity by MK571 (5 &micro ; M), a specific inhibitor of MRP efflux transporters, increases this toxicity of mercuric chloride nearly four-fold. Complete inhibition of MRP-mediated efflux activity with 40 &micro ; M MK571, in the presence of 500 nM mercuric chloride, results in accumulation of 63.58 &micro ; M intracellular mercury in the embryos ; 11-fold higher than control (5.73 &micro ; M). To determine whether glutathione (GSH) is involved in mercury efflux we exposed embryos to both 500 nM mercuric chloride and 500 nM GSH substrate 1-chloro-2, 4-dinitrobenzene (CDNB). We observed a four-fold increase in mercury toxicity and a two-fold increase in accumulation suggesting efflux of mercury as a GSH complex. Our results underscore the importance of ABCC/MRP transporters in protection from mercury. Future work will examine the efficacy of ABCC transporters against other forms of mercury, such as methylmercury, and the efficacy of this protective mechanism in the presence of environmentally relevant chemosensitizers.

MRP; mercury; sea urchin embryos

nije evidentirano