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)

The cyclic AMP (cAMP)-inducible promoter from the rat lactate dehydrogenase A subunit gene (LDH A) is associated with a distal negative regulatory element (LDH-NRE) that represses inherent basal and cAMP-inducible promoter activity. The element is of dyad symmetry, consisting of a palindromic sequence with two half-sites, 5'-TCTTG-3'. It represses the expression of an LDH A/chloramphenicol acetyltransferase (CAT) reporter gene in a dose-dependent, orientation- and position-independent fashion, suggesting that it is a true silencer element. Uniquely, it selectively represses cAMP-responsive element (CRE)-dependent transcription but has no effect on promoters lacking a CRE sequence. The repressing action of LDH-NRE could be overcome by cotransfection with LDH A/CAT vector oligonucleotides containing either the LDH-NRE or CRE sequence. This suggests that the reversal of repression was caused by the removal of functional active, limiting transacting factors which associate with LDH-NRE as well as with CRE. Gel mobility shift, footprinting, and Southwestern blotting assays demonstrated the presence of a 69-kDa protein with specific binding activity for LDH-NRE. Additionally, gel supershift assays with anti-CREB and anti-Fos antibodies indicate the presence of CREB and Fos or antigenically closely related proteins with the LDH-NRE/protein complex. We suggest that the LDH-NRE and CRE modules functionally interact to achieve negative modulation of cAMP-responsive LDH A transcriptional activity.
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PMID:Identification of a silencer module which selectively represses cyclic AMP-responsive element-dependent gene expression. 756 66

We examined the effect of cyclical mechanical stretch on the regulation of cardiac myosin heavy chain genes using an isolated neonatal rat cardiocyte culture system. Cultured cardiocytes grown on a flexible membrane were deformed by vacuum to 20% of maximum elongation, at 60 cycles/min in a serum-free medium. Cyclical stretch did not cause myocyte damage as assessed by supernatant LDH measurement and trypan blue exclusion test. The levels of myosin heavy chain (MyHC) mRNA increased as early as 1 h after stretch, reaching 12-fold over the control in 24 h, as shown by Northern blot analysis. However, the proximal 5'-flanking regions of the alpha- and beta-MyHC gene which were linked to chloramphenicol acetyltransferase (CAT) reporter gene did not exhibit enhanced CAT activity following cyclical stretch. Deletion of the chimeric constructs to shorten the 5'-flanking regions of the MyHC genes generated by polymerase chain reaction amplification did not enhance the CAT activity under cyclical stretch. This finding suggests that the stretch-response element of the alpha- and beta-MyHC gene promoter is probably not present in the proximal region of either the alpha- or beta-MyHC genes.
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PMID:Regulation of human cardiac myosin heavy chain genes by cyclical mechanical stretch in cultured cardiocytes. 775 35

Two Toxoplasma gondii genes were characterized that are differentially expressed during the parasite's life cycle. The genes named LDH1 and LDH2, respectively, encode polypeptides similar to the enzyme lactate dehydrogenase (LDH; L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) from a variety of organisms. They show 64.0% nucleotide identity in the coding region and both have an intron at the same relative position. The deduced amino acid sequences of LDH1 and LDH2 share 71.1% identity. LDH1 and LDH2 are most similar to an LDH of Plasmodium falciparum (46.5% and 48.5% amino acid identities, respectively). The mRNA of LDH2 was only detected in the bradyzoite stage, while the mRNA of LDH1 was detected in both the bradyzoite and tachyzoite stages. However, by isoelectric focusing and immunoblot analysis, only one LDH isoform was found to be expressed in each stage. Furthermore, the expression of a reporter gene carrying chloramphenicol acetyltransferase (CAT) coding sequence and the putative LDH2 promoter sequence was significantly up-regulated by growing parasites in tissue culture in media with alkaline pH (pH 8.2, a condition known to induce the expression of bradyzoite-specific antigens), while the expression of a CAT reporter construct carrying the putative LDH1 promoter sequence was down-regulated by similar treatment. These results indicate that LDH expression is developmentally regulated in T. gondii and suggest a possible correlation between stage conversion and alteration in carbohydrate or energy metabolism in this parasite.
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PMID:Toxoplasma gondii expresses two distinct lactate dehydrogenase homologous genes during its life cycle in intermediate hosts. 901 46