Skip Navigation



ToxSci Advance Access published online on September 14, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi328
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
88/2/630    most recent
kfi328v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Lash, L. H.
Right arrow Articles by Zalups, R. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lash, L. H.
Right arrow Articles by Zalups, R. K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received July 28, 2005
Accepted September 13, 2005

Systems Toxicology

Role of Organic Anion and Amino Acid Carriers in Transport of Inorganic Mercury in Rat Renal Basolateral Membrane Vesicles: Influence of Compensatory Renal Growth

Lawrence H. Lash 1*, Sarah E. Hueni 1, David A. Putt 1, and Rudolfs K. Zalups 2

1 Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan 48201 USA
2 Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, Georgia 31207 USA

* To whom correspondence should be addressed.
Lawrence H. Lash, E-mail: l.h.lash{at}wayne.edu


  Abstract

Susceptibility to renal injury induced by inorganic mercury (Hg2+) increases significantly as a result of compensatory renal growth (following reductions of renal mass). We hypothesize that this phenomenon is related, in part, to increased basolateral uptake of Hg2+ by proximal tubular cells. To determine the mechanistic roles of various transporters, we studied uptake of Hg2+, in the form of biologically relevant Hg2+-thiol conjugates, using basolateral membrane (BLM) vesicles isolated from the kidney(s) of control and uninephrectomized (NPX) rats. Binding of Hg2+ to membranes, accounted for 52-86% of total Hg2+ associated with membrane vesicles exposed to HgCl2, decreased with increasing concentrations of HgCl2, and decreased slightly with the presence of sodium ions. Conjugation of Hg2+ with thiols (glutathione, L-cysteine (Cys), N-acetyl-L-cysteine) reduced binding by more than 50%. Under all conditions, BLM vesicles from NPX rats exhibited a markedly lower proportion of binding. Of the Hg2+-thiol conjugates studied, transport of Hg-(Cys)2 was fastest. Selective inhibition of BLM carriers implicated the involvement of organic anion transporter(s) (Oat1 and/or Oat3; Slc22a6 and Slc22a8), amino acid transporter system ASC (Slc7a10), the dibasic amino acid transporter (Slc3a1), and the sodium-dicarboxylate carrier (SDCT2 or NADC3; Slc13a3). Uptake of each mercuric conjugate, when factored by membrane protein content, was higher in BLM vesicles from NPX rats, with specific increases in transport by the carriers noted above. These results support the hypothesis that compensatory renal growth is associated with increased uptake of Hg2+ in proximal tubular cells and we have identified specific transporters involved in the process.

Keywords: Mercury-thiol conjugates; kidney; basolateral membrane vesicles; transport; organic anion transporters; amino acid transporters; compensatory renal growth.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Toxicol SciHome page
L. H. Lash, D. A. Putt, and R. K. Zalups
Influence of Compensatory Renal Growth on Susceptibility of Primary Cultures of Renal Cells to Chemically Induced Injury
Toxicol. Sci., December 1, 2006; 94(2): 417 - 427.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.