A comparison of the suppression of human transferrin synthesis by lead and lipopolysaccharide
| Autor: | Christi A. Walter, Edna V. Rivera, Katrina M. Barnum-Huckins, Gwen S. Adrian, Erle K. Adrian, Frank J. Weaker, Andrew O. Martinez, Damon C. Herbert |
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| Rok vydání: | 1997 |
| Předmět: |
Genetically modified mouse
Chloramphenicol O-Acetyltransferase Lipopolysaccharides Carcinoma Hepatocellular Lipopolysaccharide Transgene Recombinant Fusion Proteins Transferrin receptor Mice Transgenic Biology Toxicology chemistry.chemical_compound Mice Albumins Organometallic Compounds Tumor Cells Cultured Animals Humans RNA Messenger Acute-Phase Reaction chemistry.chemical_classification Liver Neoplasms Albumin Acute-phase protein Transferrin Complement C3 Molecular biology chemistry Biochemistry Lead Liver Lead acetate |
| Zdroj: | Toxicology. 118(1) |
| ISSN: | 0300-483X |
| Popis: | Transferrin, as the major iron-transport protein in serum and other body fluids, has a central role in managing iron the body receives. Liver is a major site of transferrin synthesis, and in this study we present evidence that liver synthesis of human transferrin is suppressed by both the toxic metal lead and bacterial lipopolysaccharide, an inducer of the hepatic acute phase response. The responses of intact endogenous transferrin in the human hepatoma cell line HepG2 and chimeric human transferrin-chloramphenicol acetyltransferase genes in transgenic mice were examined. In HepG2 cells, 35S-transferrin protein synthesis and mRNA levels were suppressed by 100 microM and 10 microM lead acetate as early as 24 h after the initial treatment. Yet, synthesis of two proteins known to respond in the hepatic acute phase reaction, complement C3 and albumin, was not altered by the lead treatment. In transgenic mouse liver, lead suppressed expression of chimeric human transferrin genes at both the protein and mRNA levels, but LPS only suppressed at the protein level. The study indicates that lead suppresses human transferrin synthesis by a mechanism that differs from the hepatic acute phase response and that lead may also affect iron metabolism in humans by interfering with transferrin levels. |
| Databáze: | OpenAIRE |
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