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)

30A5 preadipocytes, derived from 10T1/2 mouse fibroblasts, can be induced to differentiate into adipocytes by hormone treatment. In this paper, we introduce a modified procedure to induce differentiation of 30A5 cells by pretreatment with cAMP for a brief period or by a "nutrition deprivation" pretreatment, followed by incubation in medium containing insulin. These procedures accelerate the differentiation of the preadipocytes, so that the cells are fully differentiated within 4 days instead of the 7-8 days normally required. This differentiation is accompanied by the early induction of acetyl-CoA carboxylase (ACC). ACC catalyzes the rate-limiting step in the biogenesis of long chain fatty acids. To analyze the relationship between cAMP and insulin action in the induction of ACC and cell differentiation, we identified the DNA sequences in promoter II of the ACC gene necessary for the action of insulin and cAMP. Chimeric genes between different fragments of the ACC promoter and the promoterless chloramphenicol transacetylase (CAT) gene were constructed, and stable clones containing these chimeric genes were obtained. By analyzing the CAT activities in these stable clones, we established that insulin action in inducing ACC and cell differentiation requires prior treatment of cells with cAMP and the presence of specific DNA regions in the ACC promoter for cAMP action. Stable clones containing a chimeric gene which consists of DNA sequences in promoter II that are required for insulin action, thymidine kinase promoter, and the CAT gene did not respond to insulin. However, when the DNA sequences required for cAMP action were placed in this chimeric gene, it responded to insulin upon prior treatment of 30A5 cells with cAMP. Thus, cAMP and insulin, whose physiological actions generally appear to be antagonistic, are synergistically interacting in the induction of ACC and the differentiation of 30A5 cells.
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PMID:Regulation of acetyl-CoA carboxylase gene expression. Insulin induction of acetyl-CoA carboxylase and differentiation of 30A5 preadipocytes require prior cAMP action on the gene. 167 99

The effects of mono(2-ethyl-5-oxohexyl)phthalate [ME(O)HP], a di(2-ethylhexyl)phthalate (DEHP) metabolite and a potent peroxisomal inducer, on the mitochondrial beta-oxidation were investigated. In isolated rat hepatocytes, ME(O)HP inhibited long chain fatty acid oxidation and had no effect on the ketogenesis of short chain fatty acids, suggesting that the inhibition occurred at the site of carnitine-dependent transport across the mitochondrial inner membrane. In rat liver mitochondria, ME(O)HP inhibited carnitine acyltransferase I (CAT I; EC 2.3.1.21) competitively with the substrates palmitoyl-CoA and octanoyl-CoA. An analogous treatment of mouse mitochondria produced a similar competitive inhibition of palmitoyl-CoA transport whereas ME(O)HP exposure with guinea pig and human liver mitochondria revealed little or no effect. The addition of clofibric acid, nafenopin or methylclofenopate revealed no direct effects upon CAT I activity. Inhibition of transferase activity by ME(O)HP was reversed in mitochondria which had been solubilized with octyl glucoside to expose the latent form of carnitine acyltransferase (CAT II), suggesting that the inhibition was specific for CAT I. Our results demonstrate that in vitro ME(O)HP inhibits fatty acid oxidation in rat liver at the site of transport across the mitochondrial inner membrane with a marked species difference and support the idea that induction of peroxisome proliferation could be due to an initial biochemical lesion of the fatty acid metabolism.
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PMID:In vitro inhibition of carnitine acyltransferase activity in mitochondria from rat and mouse liver by a diethylhexylphthalate metabolite. 845 57

Carnitine palmitoyltransferase I (CPTI) catalyses the transfer of long chain fatty acids to carnitine for translocation across the mitochondrial inner membrane. The cDNAs of two isoforms of CPT I, termed the hepatic and muscle isoforms, have been cloned. Expression of the hepatic CPT I gene (L-CPT I) is subject to developmental, hormonal and tissue specific regulation. We have cloned the promoter of the L-CPTI gene from a rat genomic library. In the L-CPTI gene, there are two exons 5' to the exon containing the ATG that initiates translation. Exon 1 and the 5' end of exon 2 contain sequences that were not previously described in the rat L-CPTI cDNA. There is an alternatively spliced form of the L-CPTI mRNA in which exon 2 is skipped. The proximal promoter of the L-CPTI gene is extremely GC rich and does not contain a TATA box. There are several putative Sp1 binding sites near the transcriptional start site. A 190 base pair fragment of the promoter can efficiently drive transcription of luciferase and CAT (chloramphenicol acetyltransferase) reporter genes transiently transfected into HepG2 cells. Sequences in both the first intron and the promoter contribute to basal expression. Our results provide the foundation for further studies into the regulation of L-CPTI gene expression.
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PMID:Cloning and characterization of the promoter for the liver isoform of the rat carnitine palmitoyltransferase I (L-CPT I) gene. 946 13