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

Tumour necrosis factor-alpha (TNF-alpha) plays a key role in orchestrating the complex events involved in inflammation and immunity. Accordingly, TNF-alpha has been implicated in a wide range of autoimmune and infectious diseases, but also in conditions such as obesity and insulin resistance. The regulation of TNF-alpha expression in man is indicated to be partly genetically determined. We therefore screened a 1263 bp section of the proximal promoter of the TNF-alpha gene for common genetic variants affecting the transcriptional activity of the gene. Here we report the characterization of a common functional polymorphism in the promoter region of the TNF-alpha gene, a C-->A substitution at position -863. Electromobility shift assays provided evidence for a distinct difference in the binding of monocytic and hepatic nuclear factors to the -863C and -863A alleles. The rare -863A allele was associated with 31% lower transcriptional activity ( P < 0.001) in chloramphenicol acetyltransferase (CAT) reporter gene studies in human hepatoblastoma (HepG2) cells, indicating that the-863C/A polymorphism influences the basal rate of transcription of the TNF-alpha gene in vitro. Allele frequencies were 0.83/0.17 amongst 254 apparently healthy men of Swedish origin, aged 35-50 years. In 156 men, the -863C/A polymorphism was associated with the serum TNF-alpha concentration, carriers of the rare A allele having a significantly lower TNF-alpha level ( P < 0.05). It is concluded that the common-863C/A polymorphism in the promoter region of the TNF-alpha gene is functional in vitro in monocytic and hepatic cells and influences the serum TNF-alpha concentration in vivo in healthy middle-aged men.
 ...
PMID:A common functional polymorphism (C-->A substitution at position -863) in the promoter region of the tumour necrosis factor-alpha (TNF-alpha) gene associated with reduced circulating levels of TNF-alpha. 1040 Sep 91

Tumour necrosis factor (TNF)-alpha impaired insulin induction on GLUT4 mRNA in foetal brown adipocytes, as demonstrated by quantitative RT-PCR and Northern blot. We have explored the hypothesis that some effects of TNF-alpha could be mediated by the generation of ceramide, since TNF-alpha treatment induced the production of ceramide in these primary cells. A short-chain ceramide analogue, C2-ceramide, precluded insulin-induced GLUT4 mRNA accumulation and GLUT4-chloramphenicol acetyltransferase (CAT) full promoter activation. Moreover, inhibition of the ceramide biosynthesis with fumonisin B, which inhibits ceramide synthase, completely restored insulin-induced GLUT4 mRNA and protein accumulation as well as GLUT4-CAT transactivation in the presence of TNF-alpha. In consequence, TNF-alpha-induced insulin resistance on glucose uptake was completely alleviated. In addition, TNF-alpha down-regulated insulin-induced CCAAT/enhancer binding protein (C/EBP)-alpha gene expression and DNA binding activity, but fumonisin B precludes these effects. Furthermore, co-transfection with a wild-type C/EBP-alpha construct transactivates GLUT4-CAT construct. Our results indicate that de novo ceramide produced by TNF-alpha-induced insulin resistance on GLUT4 gene expression in brown adipocytes by interfering C/EBP-alpha expression, a transcription factor essential for the expression of GLUT4.
 ...
PMID:Ceramide mediates TNF-alpha-induced insulin resistance on GLUT4 gene expression in brown adipocytes. 1675 99

Tumour necrosis factor (TNF) inhibits the accumulation of acetyl CoA carboxylase (ACC) mRNA by decreasing the rate of ACC gene transcription. The ACC mRNA species found in 30A5 cells are generated from promoter II and TNF inhibits the accumulation of class 2 type mRNAs. By using 5' deletion mutants of promoter II fused to the bacterial chloramphenicol acetyltransferase (CAT) gene, the DNA mobility shift assay and the DNase I footprinting assay, the authors have identified the 30 bp from -389 to -359 as the TNF responsive element in promoter II. TNF treatment causes a decrease in the binding activity of nuclear protein(s) specific to the TNF responsive element. When the fragment containing the TNF responsive element was incorporated into the thymidine kinase promoter, the chimeric gene exhibited TNF induced inhibition of expression.
 ...
PMID:Sequences of acetyl CoA carboxylase promoter for tumour necrosis factor action. 1847 33