Journal
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
Volume 15, Issue 3, Pages 663-673Publisher
AMER SOC NEPHROLOGY
DOI: 10.1097/01.ASN.0000113553.62380.F5
Keywords
-
Categories
Funding
- NIEHS NIH HHS [R01 ES005980, R01 ES011288, ES05980, ES11288, ES012556, F32 ES012556, F32 ES012556-01, ES05157] Funding Source: Medline
Ask authors/readers for more resources
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 conjugate of cysteine, primarily 2-amino-3-(2-amino-2-carboxyethyl sulfanylmercuricsulfanyl)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-Hu-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-Hu-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available