2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bridges, C. C. Articles by Zalups, R. K. Search for Related Content PubMed PubMed Citation Articles by Bridges, C. C. Articles by Zalups, R. K.

Mercuric Conjugates of Cysteine Are Transported by the Amino Acid Transporter System b^0,+: Implications of Molecular Mimicry

Christy C. Bridges^*, Christian Bauch, François Verrey and Rudolfs K. Zalups^*

*Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, Georgia, and Institute of Physiology, University of Zürich, Zürich, Switzerland.

Correspondence to Dr. Rudolfs K. Zalups, Division of Basic Medical Sciences, Mercer University School of Medicine, 1550 College St., Macon, GA 31207. Phone: 478-301-2559; Fax: 478-301-5489; E-mail: zalups_rk{at}mercer.edu

ABSTRACT. Humans and other mammals continue to be exposed to various forms of mercury in the environment. The kidneys, specifically the epithelial cells lining the proximal tubules, are the primary targets where mercuric ions accumulate and exert their toxic effects. Although the actual mechanisms involved in the transport of mercuric ions along the proximal tubule have not been defined, current evidence implicates mercuric conjugates of cysteine, primarily 2-amino-3-(2-amino-2-carboxyethylsulfanylmercuricsulfanyl)propionic acid (Cys-S-Hg-S-Cys), as the most likely transportable species of inorganic mercury (Hg²⁺). Because Cys-S-Hg-S-Cys and the amino acid cystine (Cys-S-S-Cys) are structurally similar, it was hypothesized that Cys-S-Hg-S-Cys might act as a molecular mimic of cystine at one or more of the amino acid transporters involved in the luminal absorption of this amino acid. One such candidate is the Na⁺-independent heterodimeric transporter system b^0,+. Therefore, the transport of Cys-S-Hg-S-Cys and cystine was studied in MDCK II cells that were or were not stably transfected with b^0,+AT-rBAT. Transport of Cys-S-Hg-S-Cys and cystine across the luminal plasma membrane was similar in the transfected cells, indicating that Cys-S-Hg-S-Cys can behave as a molecular mimic of cystine at the site of system b^0,+. Moreover, only the b^0,+AT-rBAT transfectants became selectively intoxicated during exposure to Cys-S-Hg-S-Cys. These findings indicate that system b^0,+ likely contributes to the nephropathy induced by Hg²⁺ in vivo. These data represent the first direct molecular evidence for the participation of a specific transporter in the luminal uptake of a large divalent metal cation in proximal tubular cells.

This article has been cited by other articles:

				C. C. Bridges, L. Joshee, and R. K. Zalups Multidrug Resistance Proteins and the Renal Elimination of Inorganic Mercury Mediated by 2,3-Dimercaptopropane-1-Sulfonic Acid and Meso-2,3-dimercaptosuccinic Acid J. Pharmacol. Exp. Ther., January 1, 2008; 324(1): 383 - 390. [Abstract] [Full Text] [PDF]

				C. C. Bridges and R. K. Zalups System B0,+ and the Transport of Thiol-S-Conjugates of Methylmercury J. Pharmacol. Exp. Ther., November 1, 2006; 319(2): 948 - 956. [Abstract] [Full Text] [PDF]

				R. K. Zalups and S. Ahmad Handling of the Homocysteine S-Conjugate of Methylmercury by Renal Epithelial Cells: Role of Organic Anion Transporter 1 and Amino Acid Transporters J. Pharmacol. Exp. Ther., November 1, 2005; 315(2): 896 - 904. [Abstract] [Full Text] [PDF]

				R. K. Zalups and S. Ahmad Transport of N-Acetylcysteine S-Conjugates of Methylmercury in Madin-Darby Canine Kidney Cells Stably Transfected with Human Isoform of Organic Anion Transporter 1 J. Pharmacol. Exp. Ther., September 1, 2005; 314(3): 1158 - 1168. [Abstract] [Full Text] [PDF]

				C. C. Bridges and R. K. Zalups Homocysteine, System b0,+ and the Renal Epithelial Transport and Toxicity of Inorganic Mercury Am. J. Pathol., October 1, 2004; 165(4): 1385 - 1394. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673