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γ-Glutamyl Transpeptidase and l-Cysteine Regulate Methylmercury Uptake by HepG2 Cells, a Human Hepatoma Cell Line
- Source :
- Toxicology and Applied Pharmacology. 168:72-78
- Publication Year :
- 2000
- Publisher :
- Elsevier BV, 2000.
-
Abstract
- Mechanisms of methylmercury (MeHg) and inorganic mercury (Hg) uptake were examined in HepG2 cells, a human hepatoma-derived cell line. MeHg uptake was faster when it was present as the l -cysteine complex, as compared to the glutathione (GSH), CysGly, γ-GluCys, d -cysteine, N-acetylcysteine, l -penicillamine, or albumin complexes. Uptake of MeHg- l -cysteine was independent of Na+, stereoselective, and was inhibited by the amino acid transport system l substrates l -leucine, l -valine, and l -phenylalanine (5 mM). Moreover, [3H] l -leucine uptake was inhibited by MeHg- l -cysteine, suggesting that MeHg- l -cysteine is transported into HepG2 cells by an l -type amino acid carrier. Uptake of MeHg as the GSH complex (MeHg-SG) was dependent on the extracellular GSH concentration, and was diminished when cellular γ-glutamyl transpeptidase activity was inhibited. Inorganic mercury uptake was slower than that of MeHg, but was also sensitive to the type of thiol ligand present. These findings demonstrate that mercury uptake by HepG2 cells is dependent on the chemical structure of the mercury compound, the thiol ligand, and the activity of γ-glutamyl transpeptidase. γ-Glutamyl transpeptidase appears to play a key role in the disposition of MeHg-SG by facilitating the formation of MeHg- l -cysteine, which is readily transported into the cells on an amino acid-type carrier.
- Subjects :
- Pharmacology
chemistry.chemical_classification
Carcinoma, Hepatocellular
Cell Membrane
Liver Neoplasms
Phenylalanine
Mercury
gamma-Glutamyltransferase
Glutathione
Methylmercury Compounds
Membrane transport
Toxicology
Amino acid
chemistry.chemical_compound
Biochemistry
chemistry
Valine
Tumor Cells, Cultured
Thiol
Humans
Cysteine
Leucine
Subjects
Details
- ISSN :
- 0041008X
- Volume :
- 168
- Database :
- OpenAIRE
- Journal :
- Toxicology and Applied Pharmacology
- Accession number :
- edsair.doi.dedup.....06d9c063d95696d451579d996b8e80a8