RGD Reference Report - MRP2 and the handling of mercuric ions in rats exposed acutely to inorganic and organic species of mercury. - Rat Genome Database

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MRP2 and the handling of mercuric ions in rats exposed acutely to inorganic and organic species of mercury.

Authors: Bridges, CC  Joshee, L  Zalups, RK 
Citation: Bridges CC, etal., Toxicol Appl Pharmacol. 2011 Feb 15;251(1):50-8. doi: 10.1016/j.taap.2010.11.015. Epub 2010 Dec 4.
RGD ID: 11081013
Pubmed: PMID:21134393   (View Abstract at PubMed)
PMCID: PMC3028519   (View Article at PubMed Central)
DOI: DOI:10.1016/j.taap.2010.11.015   (Journal Full-text)

Mercuric ions accumulate preferentially in renal tubular epithelial cells and bond with intracellular thiols. Certain metal-complexing agents have been shown to promote extraction of mercuric ions via the multidrug resistance-associated protein 2 (MRP2). Following exposure to a non-toxic dose of inorganic mercury (Hg(2)+), in the absence of complexing agents, tubular cells are capable of exporting a small fraction of intracellular Hg(2)+ through one or more undetermined mechanisms. We hypothesize that MRP2 plays a role in this export. To test this hypothesis, Wistar (control) and TR(-) rats were injected intravenously with a non-nephrotoxic dose of HgCl(2) (0.5 mumol/kg) or CH(3)HgCl (5 mg/kg), containing [(2)(0)(3)Hg], in the presence or absence of cysteine (Cys; 1.25 mumol/kg or 12.5mg/kg, respectively). Animals were sacrificed 24 h after exposure to mercury and the content of [(2)(0)(3)Hg] in blood, kidneys, liver, urine and feces was determined. In addition, uptake of Cys-S-conjugates of Hg(2)+ and methylmercury (CH(3)Hg+) was measured in inside-out membrane vesicles prepared from either control Sf9 cells or Sf9 cells transfected with human MRP2. The amount of mercury in the total renal mass and liver was significantly greater in TR(-) rats than in controls. In contrast, the amount of mercury in urine and feces was significantly lower in TR(-) rats than in controls. Data from membrane vesicles indicate that Cys-S-conjugates of Hg(2)+ and CH(3)Hg+ are transportable substrates of MRP2. Collectively, these data indicate that MRP2 plays a role in the physiological handling and elimination of mercuric ions from the kidney.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Abcc2Ratmercury ion transport  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Abcc2  (ATP binding cassette subfamily C member 2)


Additional Information