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

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 be 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 temperaturedependence, 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-SHg-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.

Ophthalmic findings in acute mercury poisoning in adults

“…The visual field test is an indispensable diagnostic tool for glaucoma and optic nerve disease. It can also be used in the diagnosis of drug intoxications (Bridges et al, 2007;Herba et al, 2004;da Costa et al, 2008).. However, the test is subjective and the test results may be affected due to patient compliance.…”

“…It accumulates and leads to local or systemic action in the vitreous (Bridges et al, 2007;Tanan et al, 2006). The ionic mercury, carried in the blood to the retina pigment epithelium, is distributed into photoreceptors, plexiform layer, and ganglion cells (Beuter and Edwards, 2004;Bridges et al, 2007;Toimela and Tähti, 2001;Warfvinge and Bruun, 2000). Since the earliest affected cells are scotopic cells, decreased night vision may be seen as the first clinical sign.…”

Ellagic acid: Pharmacological activities and molecular mechanisms involved in liver protection

“…Hg is a toxic and hazardous metal that may exist in the environment [180,181]. Exposure to mercurial compounds induces hepatotoxicity associated with oxidative stress [182][183][184][185], generating hepatocellular defects like hepatomegaly, centrilobular hepatic steatosis [186,187], decrease in the synthesis of hepatic coagulation factors [188][189][190][191][192] and diminution in the activity of metabolic enzymes [193].…”

The Protective Effects of Tea Polyphenols and Schisandrin B on Nephrotoxicity of Mercury

“…Large populations are currently exposed to low levels of Hg owing to the use of Hg pesticides in agriculture or as components of batteries in fluorescent light bulbs. Exposure of certain organs to Hg can result in serious toxicological consequences [1,2]. Previous studies [3,4] revealed that mercuric chloride (HgCl 2 ) can lead to tubule necrosis in the kidney.…”