Transport of thiol-conjugates of inorganic mercury in human retinal pigment epithelial cells.

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Bridges CC, Battle JR, Zalups RK

Transport of thiol-conjugates of inorganic mercury in human retinal pigment epithelial cells.

Toxicol Appl Pharmacol. 2007 Jun 1;221(2):251-60. Epub 2007 Mar 23.

PubMed ID

17467761 [ View in PubMed

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Abstract

Inorganic mercury (Hg(2+)) is a prevalent environmental contaminant to which exposure to can damage rod photoreceptor cells and compromise scotopic vision. The retinal pigment epithelium (RPE) likely plays a role in the ocular toxicity associated with Hg(2+) exposure in that it mediates transport of substances to the photoreceptor cells. In order for Hg(2+) to access photoreceptor cells, it must first be taken up by the RPE, possibly by mechanisms involving transporters of essential nutrients. In other epithelia, Hg(2+), when conjugated to cysteine (Cys) or homocysteine (Hcy), gains access to the intracellular compartment of the target cells via amino acid and organic anion transporters. Accordingly, the purpose of the current study was to test the hypothesis that Cys and Hcy S-conjugates of Hg(2+) utilize amino acid transporters to gain access into RPE cells. Time- and temperature-dependence, saturation kinetics, and substrate-specificity of the transport of Hg(2+), was assessed in ARPE-19 cells exposed to the following S-conjugates of Hg(2+): Cys (Cys-S-Hg-S-Cys), Hcy (Hcy-S-Hg-S-Hcy), N-acetylcysteine (NAC-S-Hg-S-NAC) or glutathione (GSH-S-Hg-S-GSH). We discovered that only Cys-S-Hg-S-Cys and Hcy-S-Hg-S-Hcy were taken up by these cells. This transport was Na(+)-dependent and was inhibited by neutral and cationic amino acids. RT-PCR analyses identified systems B(0,+) and ASC in ARPE-19 cells. Overall, our data suggest that Cys-S-Hg-S-Cys and Hcy-S-Hg-S-Hcy are taken up into ARPE-19 cells by Na-dependent amino acid transporters, possibly systems B(0,+) and ASC. These amino acid transporters may play a role in the retinal toxicity observed following exposure to mercury.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Glutathione	Glutathione synthetase	Protein	Humans	Unknown	Not Available	Details