Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transferrin (TF) is a plasma protein that transports and is regulated by iron. The aim of this study was to characterize human TF gene sequences that respond in vivo to cellular signals affecting expression in various tissues and to iron administration. Chimeric genes were constructed containing 152, 622, and 1152 base pairs (bp) of the human TF5'-flanking region with the coding region of a reporter gene, CAT (chloramphenicol acetyltransferase), and introduced into the germ line of mice. Transgenes containing TF 5'-flanking sequences to -152 bp were expressed poorly in all tissues examined. In contrast, transgenes containing TF sequences to -622 or -1152 bp were expressed at high levels in brain and liver, greater than or equal to 1000-fold higher than tissues such as heart and testes. Liver and brain are major sites of endogenous TF mRNA synthesis, but liver mRNA levels are 10-fold higher than brain. A significant diminution of CAT enzymatic activity in liver accompanied iron administration in both TF(0.67) and TF(1.2)CAT transgenic mice, mimicking the decrease of transferrin in humans following iron overload. Levels of endogenous plasma transferrin also decreased in iron-treated transgenic mice. Transgenic mouse lines carrying human TF chimeric genes will be useful models for analyzing the regulation of human transferrin by iron and for determining the molecular basis of transferrin regulation throughout mammalian development into the aging process.
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PMID:Human transferrin. Expression and iron modulation of chimeric genes in transgenic mice. 237 97

Transferrin (TF) gene expression is tissue specific and is regulated during development. Transgenic mice have been developed which carry 1.2 or 0.67 kb of the TF 5' flanking region of the human TF gene fused to the bacterial chloramphenicol acetyltransferase (CAT) gene. The onset of expression of the chimeric human TF-CAT transgenes in liver and brain during development has been studied in these transgenic mice. In brain, the TF(0.67)CAT transgene began to express between 5 and 10 days after birth; in liver, the TF(0.67)CAT transgene was turned on between 10 and 20 days after birth. Endogenous mouse TF mRNA levels in liver and brain have also been measured during development by Northern analysis. In brain, the developmental expression pattern of the TF(0.67)CAT transgene is the same as the mouse endogenous TF gene; in liver, the transgene is turned on later than the endogenous mouse TF gene. DNA-protein mobility shift assays and DNase I footprinting analyses were conducted in the region of -621 to -409 bp of the human TF gene by using TF-CAT expressing liver nuclear extract from 27-day-old mice and nonexpressing liver nuclear extract from 7-day-old mice. The level of protein-DNA complex formation is several times higher in the expressing extracts, and the region from -481 to -463 bp of human TF gene is protected by the expressing extract but not the nonexpressing extracts. As demonstrated by this and other studies, the transgenic mouse model furnishes a unique opportunity to analyze developmental regulation of human transgenes.
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PMID:Expression of chimeric human transferrin-chloramphenicol acetyltransferase genes in liver and brain of transgenic mice during development. 843 99

One of the primary endocrine hormones that influence the onset of Sertoli cell differentiation at puberty and help maintain differentiation in the adult testis is FSH. FSH can modulate the majority of Sertoli cell differentiated functions, including stimulation of the iron-binding protein transferrin. Previous studies have shown that FSH alters the levels of cAMP and the immediate early gene c-fos. The current study was designed to investigate the transcriptional regulation of Sertoli cell differentiation by examining the actions of FSH on the promoter of the immediate early gene c-fos and the promoter of the downstream differentiated function gene transferrin. The regulation of c-fos by FSH was investigated with various chloramphenicol acetyltransferase (CAT) constructs containing segments of the c-fos promoter, such as the serum response element (SRE), cAMP response element (CRE), and AP1/phorbol ester/TPA response element (TRE), that were transfected into cultured Sertoli cells. Observations indicate that FSH can stimulate all three response elements, as well as a whole c-fos promoter construct. Interestingly, FSH was found to have a more dramatic effect on the SRE-CAT than a cAMP analog, suggesting a difference in the actions of the two agents. Gel mobility shift assays were performed to confirm the reporter gene results. Nuclear extracts of FSH-stimulated Sertoli cells caused a labeled AP1 oligonucleotide to form a DNA/protein complex (i.e., gel shift), indicating activation of the c-fos gene and binding of the c-fos/jun complex. Nuclear extracts from both FSH- and cAMP-stimulated Sertoli cells promoted similar gel shifts with SRE and CRE oligonucleotides. This observation supports the reporter gene data in indicating that FSH can influence both the SRE and CRE. A gel mobility shift assay was also performed with an oligonucleotide containing the 5'-flanking ETS domain of the SRE (ETS-SRE) that allows the formation of a ternary complex. FSH-stimulated Sertoli cell nuclear extracts were found to promote a unique ETS-SRE gel shift not present in cAMP-stimulated cells. The observations imply that FSH actions on the SRE are in part distinct from the actions of cAMP. Transferrin gene expression was examined to study the downstream regulation of Sertoli cell differentiation. CAT constructs containing deletion mutants of a 3-kb mouse transferrin promoter were used. When transfected into Sertoli cells, the 581-bp transferrin minimal promoter, previously shown to contain a CRE, had a significant response to cAMP and FSH. The 1.6-, 2.6-, and 3-kg transferrin promoter constructs also responded to FSH and cAMP to the same extent as, or to a lesser extent than, the 581-bp minimal promoter. Interestingly, the actions of FSH on the 581-bp minimal transferrin promoter were more dramatic than those of cAMP. The importance of FSH-induced c-fos in the regulation of transferrin expression was demonstrated in the current study when a c-fos antisense oligonucleotide was found to partially inhibit (50%) the ability of FSH to induce the expression of a transferrin promoter (CAT) construct. Therefore, FSH appears to act through multiple transcriptional activation pathways. The first involves cAMP and the CRE at both early-event genes (e.g., c-fos) and downstream genes (e.g., transferrin). It is likely that other pathways involve alternate signal transduction events (e.g., calcium mobilization) and promoter response elements (e.g., SRE). These multiple pathways may act in a compensatory manner to assure the ability of FSH to influence Sertoli cell differentiation and/or in a synergistic manner to amplify FSH actions.
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PMID:Transcriptional regulation of sertoli cell differentiation by follicle-stimulating hormone at the level of the c-fos and transferrin promoters. 883 93

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.
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PMID:A comparison of the suppression of human transferrin synthesis by lead and lipopolysaccharide. 907 50