Bosnjak Ivana, Uhlinger Kevin R, Heim Wesley, Smital Tvrtko, Franekić-Colić Jasna, Coale Kenneth, Epel David, Hamdoun Amro
Laboratory for Biology and Microbial Genetics, Department for Biochemical Engineering, Faculty of Food Technology and Biotechnology, University of Zagreb, 10000 Zagreb, Croatia.
Environ Sci Technol. 2009 Nov 1;43(21):8374-80. doi: 10.1021/es901677r.
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 (HgCl(2)) and organic (CH(3)HgCl) 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.
汞化合物是持久性全球污染物,会在海洋生物以及食用这些生物的人体内蓄积。虽然海洋中汞的化学循环和形态相对已得到较好描述,但控制细胞中汞的哪些形态蓄积以及为何它们会持续存在的细胞机制却鲜为人知。在本研究中,我们研究了多药外排转运在海胆(紫球海胆)胚胎中无机汞(HgCl₂)和有机汞(CH₃HgCl)差异蓄积中的作用。我们发现,抑制MRP/ABCC型转运蛋白会增加细胞内无机汞的蓄积,但对有机汞的蓄积没有影响。同样,配体GST/GSH对金属结合酶的药理学抑制显著增加了无机汞的这种抗有丝分裂效力,但对有机汞的效力没有影响。我们的结果表明,MRP介导的无机汞共轭物消除是海洋环境中发现的两种主要汞形态在蓄积和效力上存在差异的细胞基础。