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

Abstract

Inorganic mercury (Hg{sup 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{sup 2+} exposure in that it mediates transport of substances to the photoreceptor cells. In order for Hg{sup 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{sup 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{sup 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{sup 2+}, was assessed in ARPE-19 cells exposed to the following S-conjugates of Hg{sup 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{sup +}-dependent and was inhibited by neutral and cationic amino acids. RT-PCRmore » analyses identified systems B{sup 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{sup 0,+} and ASC. These amino acid transporters may play a role in the retinal toxicity observed following exposure to mercury.« less

Authors:
 [1];  [2];  [2]
  1. Division of Basic Medical Sciences, Mercer University School of Medicine, 1550 College St., Macon, GA 31207 (United States). E-mail: bridges_cc@mercer.edu
  2. Division of Basic Medical Sciences, Mercer University School of Medicine, 1550 College St., Macon, GA 31207 (United States)
Publication Date:
OSTI Identifier:
20976953
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 221; Journal Issue: 2; Other Information: DOI: 10.1016/j.taap.2007.03.004; PII: S0041-008X(07)00116-0; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CYSTEINE; EPITHELIUM; GLUTATHIONE; HOMOCYSTEINE; MERCURY; MERCURY IONS; NUTRIENTS; POLYMERASE CHAIN REACTION; RHODOPSIN; SODIUM IONS; SPECIFICITY; SUBSTRATES; TOXICITY

Citation Formats

Bridges, Christy C., Battle, Jamie R., and Zalups, Rudolfs K. Transport of thiol-conjugates of inorganic mercury in human retinal pigment epithelial cells. United States: N. p., 2007. Web. doi:10.1016/j.taap.2007.03.004.
Bridges, Christy C., Battle, Jamie R., & Zalups, Rudolfs K. Transport of thiol-conjugates of inorganic mercury in human retinal pigment epithelial cells. United States. doi:10.1016/j.taap.2007.03.004.
Bridges, Christy C., Battle, Jamie R., and Zalups, Rudolfs K. Fri . "Transport of thiol-conjugates of inorganic mercury in human retinal pigment epithelial cells". United States. doi:10.1016/j.taap.2007.03.004.
@article{osti_20976953,
title = {Transport of thiol-conjugates of inorganic mercury in human retinal pigment epithelial cells},
author = {Bridges, Christy C. and Battle, Jamie R. and Zalups, Rudolfs K.},
abstractNote = {Inorganic mercury (Hg{sup 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{sup 2+} exposure in that it mediates transport of substances to the photoreceptor cells. In order for Hg{sup 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{sup 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{sup 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{sup 2+}, was assessed in ARPE-19 cells exposed to the following S-conjugates of Hg{sup 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{sup +}-dependent and was inhibited by neutral and cationic amino acids. RT-PCR analyses identified systems B{sup 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{sup 0,+} and ASC. These amino acid transporters may play a role in the retinal toxicity observed following exposure to mercury.},
doi = {10.1016/j.taap.2007.03.004},
journal = {Toxicology and Applied Pharmacology},
number = 2,
volume = 221,
place = {United States},
year = {Fri Jun 01 00:00:00 EDT 2007},
month = {Fri Jun 01 00:00:00 EDT 2007}
}