Multidrug Efflux Transporters Limit Accumulation of Inorganic, but Not Organic, Mercury in Sea Urchin Embryos

Abstract

Mercuric compounds are persistent global pollutants that accumulate in marine organisms and in humans who consume them. While the chemical cycles and speciation of mercury in the oceans are relatively well described, the cellular mechanisms that govern which forms of mercury accumulate in cells and why they persist are less understood. In this study we examined the role of multidrug efflux transport in the differential accumulation of inorganic (HgCl2) and organic (CH3HgCl) mercury in sea urchin (Strongylocentrotus purpuratus) embryos. We found that inhibition of MRP/ABCC-type transporters increases intracellular accumulation of inorganic mercury but had no effect on accumulation of organic mercury. Similarly, pharmacological inhibition of metal conjugating enzymes by ligands GST/GSH significantly increases this antimitotic potency of inorganic mercury, but had no effect on the potency of organic mercury. Our results point to MRP-mediated elimination of inorganic mercury conjugates as a cellular basis for differences in the accumulation and potency of the two major forms of mercury found in marine environments.

Developmental effects of two different copper oxide nanomaterials in sea urchin (Lytechinus pictus) embryos

“…A high intracellular concentration of Cu 2+ can overwhelm the natural defenses against heavy metals, such as conjugation and effluxing through membrane transporters (Cole & Deeley, 2006). Commercial nano-CuO has been shown to increase the concentration of copper inside sea urchin embryos and inhibit the activity of ABC efflux transporters at low, nontoxic nano-CuO concentrations creating chemosensitization where other toxic chemicals become more toxic due to inhibition of efflux transport (Bosnjak et al, 2009;Wu et al, 2015). Furthermore, synthesized nano-CuO can chelate short chain protein and polypeptides, causing a decreased detoxification activity that can led to a higher toxicity compared with commercial nano-CuO (Joshi et al, 2012).…”

Localization and Substrate Selectivity of Sea Urchin Multidrug (MDR) Efflux Transporters

“…Although MDR-like activity and homologous transporters have been described in several model organisms including worms (5), flies (6,7), fishes (8,9), molluscs (10), and sea urchins (11,12), the similarity of these transporters to human homologs is unclear.…”

First evidence of the P-glycoprotein gene expression and multixenobiotic resistance modulation in earthworm

“…Chemicals that are capable of inhibiting the MXR mechanism should rank high among environmentally hazardous chemicals because they threaten the basic biological defence and can revert natural resistance to disease (7,9,12,16,17). In addition, environmental samples expressing reverse MXR potential should be monitored and controlled.…”

“…The most studied efflux transporter proteins involved in the so-called multixenobiotic resistance (MXR) mechanism are ATP-binding cassette (ABC) transporters. These transmembrane proteins, present in all living organisms, interact with a wide number of chemicals, including xenobiotics, and pump them across the cell membrane, preventing their accumulation in the cell (8)(9)(10).…”